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1988 Fluoride Abstracts. Part 1.
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Acta Neuropathol (Berl) 1988;76(6):564-73
Significance of lymphocytes and blood vessel changes for edema formation in polyradiculoneuritis.
Seitz RJ, Neuen-Jacob E, Wechsler W.
Abteilung fur Neurologie, Universitat Dusseldorf, Federal Republic of Germany.
Human sural nerve biopsies of eight cases with acute, subacute and chronic polyradiculoneuritis were studied by means of immunohistochemistry to characterize the inflammatory infiltrates. In addition, the structural changes of the endoneurial blood vessels were examined by electron microscopy, since both factors are likely to contribute to disturbances of the blood-nerve barrier. By use of six monoclonal antibodies, it was shown that the inflammatory infiltrates in cases with more acute polyradiculoneuritis are predominantly recruited by Leu 3a- and Leu 4-positive T lymphocytes. In more chronic polyradiculoneuritis beside of few Leu 3a-positive and Leu 4-positive T lymphocytes also B cells occurred. Leu M3-positive macrophages were detected in all cases with fluoride myelin degeneration. Since immunoreactivity for antigens of the HLA-D-locus (Leu-HLA-DR and Leu 10) were present on the infiltrating mononuclear cells, it can be postulated that they represent active and immunocompetent cells. Ultrastructurally, the amount of pinocytotic vesicles in the endothelial cells of the endoneurial blood vessels was increased. Moreover, a prominent folding of the luminal and abluminal surface of vascular endothelial cells and diminution of the intercellular tight junctions were observed. These findings appear suitable to explain the increased leakage of serum proteins across the blood-nerve barrier in polyradiculoneuritis sharing general features of cell-mediated immunity.
PMID: 3201919 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2845082&dopt=AbstractJ Med Chem 1988 Oct;31(10):1972-7
Syntheses and adrenergic activities of ring-fluorinated epinephrines.
Adejare A, Gusovsky F, Padgett W, Creveling CR, Daly JW, Kirk KL.
Laboratory of Chemistry, National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
The study of chemical and biological effects of fluorine substitution on the aromatic ring of catecholamines has now been extended to epinephrine (Epi). 2- and 6-fluoroepinephrines (2-FEpi and 6-FEpi) have been synthesized. Fluorine substitution on the 2- or 6-carbon of the aromatic ring alters the selectivity of epinephrine toward alpha- and beta-adrenergic receptors, similar in manner to the change in selectivity seen with norepinephrine (NE). Thus, 2-FEpi is a relatively selective beta-adrenergic ligand, while 6-FEpi is a relatively selective alpha-adrenergic ligand. Fluorine substitution of Epi also can markedly increase potency at either alpha- or beta-adrenergic receptors.
PMID: 2845082 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3138993&dopt=AbstractBiochem Biophys Res Commun 1988 Sep 15;155(2):664-9
Fluoride inhibits agonist-induced formation of inositol phosphates in rat cortex.
Godfrey PP, Watson SP.
Department of Clinical Pharmacology, Radcliffe Infirmary, Oxford, United Kingdom.
Sodium fluoride inhibited carbachol, 5-hydroxytryptamine and noradrenaline stimulated formation of inositol phosphates in rat cerebral cortex. For example, carbachol (1 mM) induced a 337% increase of inositol phosphates above basal in 30 min which was reduced to 69% in the presence of NaF (10 mM). The IC50 for NaF was approximately 1.5 mM and inhibition was mediated by a decrease in maxima of the carbachol dose response curve rather than a shift to the right. This inhibitory action was not mimicked by NaBr or NaI, or by agents which increase cAMP. Inhibition did not appear to result from a toxic action of NaF since it had no effect on the formation of inositol phosphates by high K+; moreover, in higher concentrations NaF stimulated phospholipase C activity. Since fluoride ions are known to activate G-proteins in the concentrations used in this study, these results may indicate the existence of a novel G-protein linked to receptor inhibition of phospholipase C.
PMID: 3138993 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2846782&dopt=AbstractJ Neurochem 1988 Dec;51(6):1731-6
Modulation of phosphoinositide hydrolysis by NaF and aluminum in rat cortical slices.
Jope RS.
Department of Pharmacology and Neuropsychiatry Research Program, University of Alabama, Birmingham.
NaF stimulated phosphoinositide hydrolysis in rat cortical slices. The production of [3H]inositol monophosphate was rapid for the first 15 min of incubation with NaF, followed by a plateau. The major product detected was [3H]inositol monophosphate, although significant amounts of [3H]inositol bisphosphate and [3H]inositol trisphosphate were also produced. The stimulation of [3H]inositol monophosphate production by NaF was concentration dependent between 2 and 20 mM NaF. Addition of 10 or 100 microM AlCl3 or aluminum maltol did not alter the effect of NaF, whereas at 500 microM, these aluminum preparations resulted in significant inhibition. Increasing the concentration of K+ from 5 to 20 mM potentiated [3H]inositol monophosphate production induced by carbachol but not by NaF. Incubation with 1 microM phorbol 12-myristate 13-acetate, a phorbol ester, inhibited carbachol-induced, but not NaF-induced, [3H]inositol monophosphate production. These results further support the hypothesis that a guanine nucleotide binding protein that can be activated by NaF is involved in phosphoinositide hydrolysis in brain. The use of NaF provides a means to bypass receptors to study intracellular regulatory sites of phosphoinositide metabolism without disrupting cells.
PMID: 2846782 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3398820&dopt=AbstractNeurotoxicol Teratol 1988 Mar-Apr;10(2):127-33
Subchronic neurotoxicity in rats of the structural fumigant, sulfuryl fluoride.
Mattsson JL, Albee RR, Eisenbrandt DL, Chang LW.
Health and Environmental Sciences, Dow Chemical Co., Midland, MI 48674.
Inhalation exposure of male and female Fischer 344 rats to sulfuryl fluoride [Vikane (Dow Chemical Company) gas fumigant] at 300 ppm for 6 hr/day, 5 days week, for 13 weeks caused diminished weight gain, dental fluorosis, a slight decrease in grooming, decreased flicker fusion threshold, slowing of flash, auditory and somatosensory evoked potentials, mild nasal and pulmonary inflammation, mild kidney effects, and mild vacuolation in the brain. Auditory brainstem responses (ABRs) and brain histology were evaluated two months postexposure in 2 male and 2 female rats. Both the ABRs and brain histology were within normal limits at this time, indicating that these treatment effects were, to at least a great extent, reversible. Exposure to 100 ppm resulted in dental fluorosis and very minor slowing of some evoked responses; all other measures, including brain histology, were normal. No treatment effects were noted at 30 ppm.
PMID: 3398820 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3224306&dopt=AbstractCell Biol Toxicol 1988 Sep;4(3):311-24
Transforming activities of sodium fluoride in cultured Syrian hamster embryo and BALB/3T3 cells.
Lasne C, Lu YP, Chouroulinkov I.
Institut de Recherches Scientifiques sur le Cancer, Villejuif, France.
The transforming activity of sodium fluoride was studied in the SHE and the BALB/3T3 cell culture systems. Initiating and promoting activities were then investigated by means of the orthogonal methodology. Sodium fluoride was found to induce morphological transformation of SHE cells seeded on a feeder layer of X-irradiated cells at high concentrations (75-125 micrograms/ml). When the cells were seeded in the absence of a feeder-layer, the transformation frequencies increased in a dose-dependent manner with the concentrations of sodium fluoride ranging from 0 to the highly toxic concentration of 200 micrograms/ml. In the BALB/3T3 cell system, sodium fluoride was negative in the standard Kakunaga procedure, while through the experiment designed by table L8 (2(7] of the orthogonal method, an initiating-like effect and a weak promoting activity were detected within the concentrations ranging from a 25 micrograms/ml to a 50 micrograms/ml concentration which is highly toxic for BALB/3T3 cells. From these results, it is suggested that, besides a genetic mode of action, sodium fluoride could possibly act through a non-genotoxic mechanism.
PMID: 3224306 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2828807&dopt=AbstractLife Sci 1988;42(7):829-40
Sex steroid regulation of beta-adrenergic sensitive adenylate cyclase in rabbit myometrial cells in primary culture.
Boulet AP, Fortier MA.
Centre Hospitalier de l'Universite Laval, Quebec, Canada.
Cyclic adenosine 3'-5'-monophosphate (cAMP) is the likely mediator of myometrial relaxation induced by agents like isoproterenol and relaxin. In vivo, the relaxation response to beta-adrenergic catecholamines is modulated by estradiol (E2) and progesterone (P) during the estrous cycle and pregnancy. However, it is still debated whether that regulation occurs via a direct action on myometrial cells or indirectly through modulation of adrenergic neurotransmitters. We have studied the properties of adenylate cyclase in primary cultures of smooth muscle cells isolated from rabbit myometrium. Adenylate cyclase activity increased with time in culture reaching a maximum on day 6. The cultured cells had basal activity which could be stimulated by guanosine triphosphate (GTP, 2.3 fold), its non-hydrolysable analogue guanylyl-imido-diphosphate (GPP[NH]p, 8.3 fold) and sodium fluoride (NaF, 15.7 fold). Isoproterenol (Iso) and prostaglandin E2 (PGE2) stimulated adenylate cyclase activity to the same level (4 fold) and required the presence of exogenous GTP. Sex steroid treatment did not affect basal activity or its stimulation by guanyl nucleotides, PGE2 or NaF. However, the adenylate cyclase response to Iso was significantly affected by E2 and/or P treatment. E2 treatment for 6 days diminished the sensitivity 10 fold (from 10 nM to 100 nM) while E2 for 3 days followed by P for 3 days increased it 10 fold (to 1 nM). Maximal response was not affected by treatment with E2 for 6 days but was diminished by 43% (p less than 0.001) when P was added alone and increased by 63% (p less than 0.001) when P was added following E2 pretreatment. Our results demonstrate that sex steroids can alter beta-adrenergic response in vitro by a direct action on myometrial cells.
PMID: 2828807 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2833100&dopt=AbstractAm J Med Sci 1988 Mar;295(3):178-82
Stimulation of cAMP accumulation and superoxide production in human neutrophils and monocytes.
Shahed AR, Zhang W, Antony VB.
Department of Medicine, Indiana University School of Medicine, VA Medical Center, Indianapolis 46202.
The effect of sodium fluoride (NaF) on superoxide generation and cyclic adenosine monophosphate (cAMP) levels in human neutrophils and monocytes was investigated. NaF (greater than 10 mM) stimulated superoxide (O2-) production in both cell types in a time dependent manner. NaF (0.5 to 20 mM) increased cAMP levels by 1.5- to 3.-fold in both neutrophils and monocytes. Increases in cAMP levels were time-dependent; the maximal level was attained within 5 minutes after the addition of NaF, and cAMP levels remained elevated for up to 10 minutes. Only high concentrations of NaF (10 and 20 mM) increased both cAMP levels and O2- production. Therefore, a direct role of cAMP in O2- generation is not likely. It is speculated that since NaF (greater than 10 mM) can complex with extracellular Ca++, and thus reduce free Ca++ concentration required for O2- generation, a NaF-dependent increase in cAMP may restore cytosolic free Ca++ by mobilizing intracellular stores of Ca++. Further, in view of the proposed involvement of a phosphorylation-dephosphorylation mechanism in the regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, we speculate that NaF, by inhibiting phosphoprotein phosphatase activity, may indirectly activate the NADPH oxidase system and thus superoxide generation.
PMID: 2833100 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2829901&dopt=AbstractBiochem Biophys Res Commun 1988 Feb 15;150(3):955-64
Fluoride can activate the respiratory burst independently of Ca2+, stimulation of phosphoinositide turnover and protein kinase C translocation in primed human neutrophils.
Della Bianca V, Grzeskowiak M, Dusi S, Rossi F.
Institute of General Pathology, University of Verona, Italy.
Evidences have been provided in our laboratory that in neutrophils different signal transduction sequences for the activation of O2(-)-forming NADPH oxidase can be triggered by the same stimulus (Biochem. Biophys. Res. Commun. 1986, 135, 556-565; 1986, 135, 785-794; 1986, 140, 1-11). The results presented here show that the transduction sequence triggered by fluoride via dissociation of G-proteins and involving messengers produced by stimulation of phosphoinositide turnover, Ca2+ changes and translocation of protein kinase C from the cytosol to the plasmamembrane, can be bypassed when a primed state of neutrophils is previously induced. In fact:
i) fluoride causes a pertussis toxin insensitive and H-7 sensitive respiratory burst in human neutrophils, which is linked to the activation of hydrolysis of PIP2, rise in [Ca2+]1 and translocation of PKC. In Ca2+-depleted neutrophils these responses to fluoride do not occur and are restored by addition of CaCl2.
ii) The pretreatment of Ca2+-depleted unresponsive neutrophils with non stimulatory doses of PMA restores the activation of the NADPH oxidase by fluoride but not the turnover of phosphoinositides and PKC translocation. The nature of the alternative transduction sequence, the reactions different from phospholipase C activated by G-protein for the alternative sequence and the role of these discrete pathways for NADPH oxidase activation are discussed.
PMID: 2829901 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3353987&dopt=AbstractToxicol Appl Pharmacol 1988 Mar 15;92(3):390-401
- Trifluoroethanol and its oxidative metabolites: comparison of in vivo and in vitro effects in rat testis.
Lloyd SC, Blackburn DM, Foster PM.
Imperial Chemical Industries PLC, Central Toxicology Laboratory, Macclesfield, Cheshire, United Kingdom.
Trifluoroethanol (TFE) and trifluoroacetaldehyde (TFALD) produced a reduction in testis weight 3 days after a single oral dose of 10 mg/kg. In contrast, administration of trifluoroacetic acid (TFAA) caused no observable testicular effects. Reduction in testis weight was accompanied by morphological changes, involving specific damage to pachytene and dividing spermatocytes, and round spermatids. In an in vitro Sertoli/germ cell co-culture system, only TFALD was found to produce dose-related effects at concentrations of 10(-3) and 10(-4) M. There was increased germ cell loss from the cultures, particularly loss of pachytene and dividing spermatocytes, accompanied by leakage of the pachytene spermatocyte marker enzyme, lactate dehydrogenase-X. TFE and TFAA did not produce these effects in the culture system at concentrations equimolar with TFALD. These results suggest that TFALD may play a critical role in the development of the testis lesion seen with TFE in vivo. The effects seen both in vivo and in vitro were remarkably similar to those previously reported for another substituted alcohol and its metabolites, ethylene glycol monomethyl ether. It is postulated that the two series of compounds may have a similar mode of action on rat testis.
PMID: 3353987 [PubMed - indexed for MEDLINE]
Fluoride 1988; 21(1):32-38Ultrastructural findings in liver, kidneys, thyroid gland and cardiac muscle of rabbits following sodium fluroide administration
Z Chongwan * and H Daijei
* Department of Histology and Embryology, Guiyang Medical College, Guizhou, China
Summary: After seven months administration of 10 mg or 50 mg sodium fluroide/day/kg body weight to albino rabbits, their liver, kidneys, thyroid glands and cardiac muscles were studied under transmission electron microscope. Swelling of mitochrondria enlargement of SER cisterns and decrease of RNA granules and RER in these organs were the primary findings. Fluorosis might primarily be an organelle disease which leads to a series of biochemical, pathological and clinical abnormalities.
Fluoride 1988; 21(3):127-130Biochemical effects of fluoride on thyroid gland during experimental fluorosis
Shashi
Department of Zoology, Punjabi University, Patiala, India
Summary: Fluorosis leads to fat accumulation in the thyroid gland, hyperlipidemia and hypertriglyceridemia. The administration of sodium fluroide in the concentrations of 5, 10, 20 and 50 mg/kg b.w./day to normal rabbits for 100 days increased the lipid components, total lipids and triglycerides in thyroid gland. The increase in content was highly siginificant compared to controls. The level of free fatty acids was significantly reduced in thyroid gland of fluroide-treated rabbits.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2897096&dopt=AbstractNeurosci Lett 1988 Mar 31;86(2):207-12
Increase in the stimulation-induced overflow of excitatory amino acids from hippocampal slices: interaction between low glucose concentration and fluoroacetate.
Szerb JC, O'Regan PA.
Department of Physiology and Biophysics, Dalhousie University, Halifax, Canada.
To see whether the enhanced evoked release of aspartate and glutamate in the presence of low glucose concentration is due to a decreased glial uptake, the electrical-field stimulation induced release of aspartate and glutamate was measured in rat hippocampal slices in the presence of 5 or 0.2 mM glucose and of graded concentrations of fluoroacetate, a specific inhibitor of glial tricarboxylic acid cycle. In 5 mM glucose, fluoroacetate increased the overflow of both excitatory amino acids equally in a dose-dependent manner, with a maximal effect obtained at 2 mM. This maximal increase of glutamate overflow was about the same as caused by 0.2 mM glucose, but low glucose increased aspartate overflow 5 times more than did fluoroacetate. Fluoroacetate failed to increase any further the large evoked overflow of either glutamate or aspartate induced by 0.2 mM glucose. The absence of an additive effect of fluoroacetate and of low glucose suggests that under both conditions the increased overflow of glutamate is due to a reduced glial uptake. In low glucose an increased synthesis also contributes to the additional large release of aspartate.
PMID: 2897096 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3205432&dopt=AbstractNeurotoxicology 1988 Summer;9(2):223-33
Histopathological assessment of triphenyl phosphite neurotoxicity in the hen.
Carrington CD, Brown HR, Abou-Donia MB.
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
The signs of neurotoxicity observed in the cat and the rat following single or multiple doses of the phosphorous acid ester triphenyl phosphite (TPP) have been reported to differ from the syndrome known as organophosphorous compound induced delayed neuropathy (OPIDN) caused by some phosphoric acid esters. Since the hen is the test animal traditionally used to test compounds for OPIDN, we chose to study the neurotoxicity of single, subcutaneous doses of TPP using the hen. TPP (1000 mg/kg) produced progressive ataxia and paralysis which developed 5-10 days after dosing. The clinical signs were accompanied by axonal damage in the lateral columns of the spinal cord and peripheral nerve. Similar signs were observed following neurotoxic doses of the OPIDN-causing agents tri-o-cresyl phosphate (TOCP) or diisopropyl phosphorofluoridate (DFP). In addition, TPP caused damage to axons in the brain and gray matter of the spinal cord, and chromatolysis and neuronal necrosis were frequently observed in the spinal cord. These latter areas were not affected by TOCP or DFP. The minimum neurotoxic dose of TPP was found to be 500 mg/kg. Prior administration of phenylmethylsulfonyl fluoride (PMSF) reduced the incidence of damage to the peripheral nerve of animals dosed with TPP, but did not prevent toxic effects on the cell bodies in the spinal cord or the clinical effects. The results of this study indicate that TPP causes neuronal damage in addition to the axonal damage observed with OPIDN. Therefore, we conclude that two distinct mechanisms underlie the neurotoxicity of TPP.
PMID: 3205432 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2836175&dopt=AbstractEndocrinology 1988 Jun;122(6):2833-9
Fluoride stimulates the accumulation of inositol phosphates, increases intracellular free calcium, and inhibits parathyroid hormone release in dispersed bovine parathyroid cells.
Shoback DM, McGhee JM.
Endocrine Research Unit, San Francisco Veterans Administration Medical Center, California 94121.
The stimulation of polyphosphoinositide (PPI) turnover is associated with cellular activation and hormone secretion in numerous systems. GTP-binding proteins appear to couple receptors to phospholipase-C-mediated PPI breakdown. We assessed the effects of fluoride, an activator of GTP-binding proteins, on inositol phosphate accumulation, intracellular free Ca2+ [(Ca2+)i], cAMP content, and PTH release in dispersed bovine parathyroid cells. Sodium fluoride (5-30 mM) produced marked dose-dependent increases in inositol phosphates. With anion exchange HPLC, we confirmed that 30 mM fluoride stimulated a rapid increase in 1,4,5-inositol trisphosphate, a potent Ca2+-mobilizing compound. Using the Ca2+-sensitive probe fura-2, we determined that 30 mM fluoride increased [Ca2+]i from 339 +/- 9 to 650 +/- 39 nM (n = 8) within 30-60 sec at 1 mM extracellular Ca2+. After the depletion of extracellular Ca2+ by the addition of 1 mM EGTA, 30 mM fluoride increased [Ca2+]i 45 +/- 9% (n = 4), indicating that fluoride can mobilize intracellular Ca2+ stores. Fluoride (1-30 mM) also inhibited PTH release in dose-dependent fashion. Fluoride (30 mM) produced 72.8 +/- 4.2% suppression of maximal low Ca2+-stimulated PTH release comparable to the 83.7 +/- 3.7% inhibition by 2.0 mM extracellular Ca2+. Since changes in both [Ca2+]i and cAMP regulate PTH release, we measured the effect of fluoride on intracellular cAMP. Fluoride did not detectably change basal cAMP content, but it reduced forskolin-stimulated increases in cAMP. We conclude that fluoride may activate at least two GTP-dependent processes in parathyroid cells, resulting in PPI breakdown and cAMP accumulation. While both may contribute to the fluoride-induced suppression of PTH release, our findings suggest that the stimulation of PPI turnover leads to inhibition of PTH secretion.
PMID: 2836175 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2463739&dopt=AbstractJ Bone Miner Res 1988 Jun;3(3):279-88
Effects of fluoride on parathyroid hormone secretion and intracellular second messengers in bovine parathyroid cells.
Chen CJ, Anast CS, Brown EM.
Endocrine Division, Children's Hospital, Boston, MA.
Fluoride ion (F-) alone or in conjunction with aluminum (Al3+) has been shown to stimulate the activity of guanine nucleotide-binding proteins (G proteins) in cell membrane preparations from a variety of cell types and in intact hepatic cells. Several studies have indicated that G proteins are involved in the regulation of parathyroid hormone (PTH) secretion. Intracellular second messengers which modulate PTH secretion (e.g., cAMP) have also been found to be regulated by G proteins. We have, therefore, employed F- as a probe to investigate the possible role of G proteins in the modulation of PTH release and the intracellular second messengers that have been implicated in the control of PTH secretion. F- produces a dose-dependent inhibition of PTH release with a maximal inhibitory effect (67%) at 5 mM. F- exerts its inhibitory effect within 5 min and the degree of suppression of PTH secretion gradually increases over 1 hr. F- (5 mM) inhibits PTH secretion at 0.5 mM Ca2+ to the level observed with 2 mM Ca2+ alone; moreover, the effects of F- and high Ca2+ are not additive. While 1 mM F- suppresses PTH secretion by only 21%, and 10 microM Al3+ has virtually no effect at all, together they inhibit PTH release approximately to the level (63% inhibition) observed with 5 mM NaF alone. In the presence of 10(-5) M dopamine, F- produces a concentration-dependent inhibition of cAMP accumulation (0.684 +/- 0.033 pmoles/10(5) cells at 0 mM F- vs. 0.256 +/- 0.048 at 5 mM F-). However, the F- -induced decrease in cAMP cannot account for the inhibition of PTH release by this agent, since addition of methylisobutylxanthine (10(-4) M) by F- -treated cells raises intracellular cAMP content above that of control cells but fails to reverse the inhibition of PTH release. The cytosolic calcium concentration in Fura-2-loaded cells increases from 210 +/- 20 nM to 340 +/- 44 nM after 5 mM F- was added to incubation media. Prior removal of extracellular Ca2+ by EGTA totally blocks the F- -induced rise in cytosolic Ca2+ without preventing the inhibition of PTH release by NaF. F- also produces a time- and dose-dependent increase in the accumulation of IP, IP2, and IP3 in cells prelabeled with [3H]inositol and incubated with 10 mM Li+, consistent with activation of phospholipase C. We conclude that F- is a potent inhibitor of PTH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)
PMID: 2463739 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3145376&dopt=AbstractLife Sci 1988;43(26):2241-7
Erratum in: Life Sci 1989;44(6):439
NaF-induced Ca2+ mobilization is dependent upon the culture density in a parathyroid hormone-responsive osteoblast-like cell line.
Kawase T, Ishikawa I, Suzuki A.
Department of Pharmacology, Niigata University School of Dentistry, Gakkocho-dori, Japan.
The effect of NaF on cytosolic free Ca2+ concentrations [( Ca2+]i) was examined in a clonal osteoblast-like cell line (MOB 3-4) loaded with Fura 2. MOB 3-4 cells in a sparse culture, which exhibited neither alkaline phosphatase (ALP) activity nor the response to parathyroid hormone (PTH), responded to NaF (0.1-10 mM) to increase [Ca2+]i transiently. In contrast, the cells in a dense culture, which exhibited both ALP activity and the response to PTH, responded to NaF (above 4 mM) to increase [Ca2+]i slowly. [Ca2+]i in osteoblasts in primary culture slowly increased in response to both NaF (above 4 mM) and PTH (3 U/ml). Thus, the sensitivity and the response of MOB 3-4 cells to NaF and PTH varied with the culture density, and high culture density matured the cells like osteoblasts in primary culture. These NaF-induced Ca2+ mobilizations were not dependent upon external Ca2+ and were enhanced by Al3+ (1 microM), whereas the PTH-induced Ca2+ mobilizations were due to Ca2+ influx. These results suggest that the maturation of MOB 3-4 cells, dependent upon the culture density, modulates intracellular signal transduction pathways and thereby alters the NaF-induced Ca2+ mobilization, and that the culture density must be taken into consideration in studying Ca2+ mobilization in such an osteoblast-like cells line as MOB 3-4 cell line.
PMID: 3145376 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2450544&dopt=AbstractBiochem Biophys Res Commun 1988 Mar 15;151(2):774-80
Synaptosomal calcium influx is activated by sodium fluoride.
Jope RS, Lally KM.
Department of Pharmacology, University of Alabama, Birmingham 35294.
Neuronal calcium channels can be modulated by changes in membrane potential or by activation of channel-associated receptors. The latter may be modulated by guanine nucleotide binding proteins. NaF, which activates guanine nucleotide binding proteins, caused a large stimulation of 45Ca2+ uptake by synaptosomes prepared from rat brain. Stimulation of 45Ca2+ influx by NaF
(i) was apparent in media containing either 5 mM-K+ or 50 mM-K+,
(ii) was slower than the fast-phase of voltage-dependent 45Ca2+ influx but continued for a longer period of time than did depolarization-induced 45Ca2+ influx, and (iii) was not mimicked or modified by a number of drugs, including ouabain, dinitrophenol, sodium azide or sodium vanadate.
These results are consistent with the hypothesis that NaF activates a guanine nucleotide binding protein associated with receptor-coupled calcium channels, resulting in stimulation of calcium influx.
PMID: 2450544 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3056628&dopt=AbstractCarcinogenesis 1988 Dec;9(12):2279-84
Sodium fluoride promotes morphological transformation of Syrian hamster embryo cells.
Jones CA, Callaham MF, Huberman E.
Biological, Environmental, and Medical Research Division, Argonne National Laboratory, IL 60439-4833.
Sequential treatment of Syrian hamster embryo (SHE) cells with a chemical carcinogen followed by sodium fluoride (NaF) resulted in a higher yield of morphologically transformed cell colonies than treatment of the cells with carcinogen alone. For example, cells treated with benzo[a]pyrene (B[a]P; 3 micrograms/ml) for 3 days, then with NaF (25 micrograms/ml) for 4 days, exhibited a transformation frequency more than six times greater than that obtained by summing the transformation frequencies from cells treated with either B[a]P or NaF alone. This enhancement/promotion of cell transformation by NaF was only expressed after the cells had been pretreated with either direct-acting carcinogens or procarcinogens. Pretreatment of the cells with noncarcinogens or weakly-acting carcinogens or administration of NaF prior to treatment with the carcinogen failed to enhance the yield of transformation. Transformation was enhanced even when the NaF treatment was delayed for several days after the carcinogen treatment. However, the continued presence of NaF was necessary for maintenance of the increased level of transformation. Removal of NaF prior to termination of the assay resulted in a reversal of the transformed clonal morphologies to a normal phenotype such that the final yield of transformants was decreased, but was still greater than that observed after carcinogen treatment alone. A similar pattern for reversibility of the transformation enhancement also occurs for the widely recognized tumor promoter phorbol 12-myristate 13-acetate (PMA). Seven different SHE cell pools were tested for sensitivity to NaF promotion following carcinogen treatment. Although the response was heterogeneous, no carcinogen-treated cell pool was refractory to the NaF-induced enhancement. A second fluorocompound, sodium monofluorophosphate (NaMFP), was also found to enhance carcinogen-induced cell transformation in a manner resembling that of NaF.
PMID: 3056628 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3123922&dopt=AbstractMutat Res 1988 Mar;195(2):127-36
Genotoxic effects of fluoride: a controversial issue.
Li YM, Dunipace AJ, Stookey GK.
Indiana University School of Dentistry, Oral Health Research Institute, Indianapolis 46202.
Fluoride is an element which is widely distributed in our environment. Its cariostatic efficacy has been well documented, and numerous studies indicate that at a concentration of 1 ppm in water, fluoride is beneficial for caries prevention and does not appear to exacerbate any diseases. Currently, more than half the American population is consuming naturally or artificially fluoridated water and efforts are being made to increase this proportion significantly. In addition, the multiple use of fluoride for dental caries prevention is clearly increasing. It is a common practice to use fluoride in a variety of delivery systems, including dentifrices, mouthrinses, pediatric supplements, and professional or self-applied topical solutions or gels as well as dental restorative materials. These dental products may contain fluoride in concentrations as high as 12,300 ppm. Increasing exposure of the population to fluoride has raised questions about the safety of this measure and has established the need for objective reappraisal. In particular, interest has developed regarding the genotoxic effects of fluoride. Unfortunately, there is, at present, only a limited amount of information available concerning the potential genotoxic effects of fluoride, and the results that have been published are contradictory and often very confusing. A review of the literature clearly indicates the importance of, and necessity for, clarifying the conflicts and controversies regarding this important issue.
Publication Types:
- Review
- Review, Academic
PMID: 3123922 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2852072&dopt=AbstractBrain Res Dev Brain Res 1988 Dec 1;44(2):269-80
Morphological and biochemical differentiation of the human medulloblastoma cell line TE671.
Siegel HN, Lukas RJ.
Division of Neurobiology, Barrow Neurological Institute, Phoenix, AZ 85013.
Cells of the human medulloblastoma clonal line TE671 exhibit polymorphism when grown in vitro in serum-supplemented medium. Under these conditions, cell numbers double every 18 h during log phase growth. These tumorigenic precursors of cerebellar interneurons are not contact-inhibited and approach densities of one million cells per cm2. TE671 cells in proliferative growth express a class of nicotinic acetylcholine receptors that are fully sensitive to functional blockade by the neurotoxin alpha-bungarotoxin (Bgt). TE671 cells grown in medium containing dibutyryl cyclic adenosine monophosphate (dbcAMP) rapidly undergo a distinctive morphological transformation characterized by neurite extension and formation of cell-cell contacts. The rate of cell division and cell saturation densities are diminished coordinately with these treatments. Sodium fluoride and forskolin induce similar changes in cell division and morphology as does dbcAMP, and these effects are potentiated by aluminum and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, respectively. The high-affinity binding of Bgt to TE671 cells also is reduced on exposure to dbcAMP in a time and dose-dependent manner. The results suggest that activation of adenylate cyclase and the concomitant elevation of intracellular cAMP levels may be involved in the morphological transformation of TE671 cells to a mature, neuronal phenotype and in changes in the level of expression of a subtype of human neuronal nicotinic receptors. These studies establish a unique, neural tube-derived model system for investigation of the mechanisms involved in these processes.
PMID: 2852072 [PubMed - indexed for MEDLINE]
Fluoride 1988; 21(2):93-99Subcellular effects of fluoride
J Elsair * and K Khelfat
* Laboratory of Medical Physiology, Institute of Medical Sciences (INESSM), Algiers, Algeria
Summary: Fluoride induces toxicological effects in different tissues when it is administered in vivo and, to a lesser degree, in vitro. The action of fluoride on subcellular components such as membranes, mitochondria, and the systems involved in protein synthesis including the nucleus, polysomes, mitodhondria, and hyaloplasm, has been reviewed.
Fluoride 1988; 21(3):149-158The effect of sodium fluroide on the growth and differentiation of human fetal osteoblasts - an in vitro study
Song XD *, Zhang WZ, Li LY, Pang ZL, Tan YB
* Tianjin Institute of Endocrinology, Tianjin, China
Summary: Human fetal osteoblast (OB) culture has been established as a model of osteofluorosis. Fluoride affects not only the morphology of osteoblasts, but also their metabolism, as shown by 45Ca uptake rate, activity of alkaline phosphatase (ALP) and cell protein. In addition, we also observed that alkaline phosphatase activity showed a biphasic pattern at different cytotoxic doses of fluoride. The preliminary explanation for these findings is discussed.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3188078&dopt=AbstractToxicol Lett 1988 Nov;44(1-2):21-9
Effect of subacute dosage of fluoride on male mice.
Pillai KS, Mathai AT, Deshmukh PB.
Jai Research Foundation, Dist Bulsar, Gujarat, India.
A sublethal concentration (one-tenth of the LD50) of fluoride (F) (5.2 mg F/kg body weight) was administered to Swiss albino mice (male) daily for 35 days. These mice showed a decrease in body weight gain, and food and water consumption. A significant decrease in red blood cell counts and an increase in white blood cell counts were seen in fluoride-administered mice. These animals also showed a decline in albumin, total protein, cholesterol, glucose and alkaline phosphatase activity in the serum. The fluoride content significantly increased in different organs of these animals. Sperm did not show any abnormalities due to fluoride toxicity.
PMID: 3188078 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2848509&dopt=AbstractBiochem J 1988 Oct 1;255(1):327-33
Fluorine compounds inhibit the conversion of active type-1 protein phosphatases into the ATPMg-dependent form.
Bollen M, Stalmans W.
Afdeling Biochemie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Belgium.
1. The modulator protein slowly converts the glycogen-bound protein phosphatase from liver, as well as its catalytic subunit, into an inactive form that requires protein kinase FA and MgATP for reactivation. The inactivation process could be completely prevented by addition of either 0.3 mM-NaF or 0.3 mM-phenylmethanesulphonyl fluoride (PMSF). The effectiveness of the proteinase inhibitor was not due to production of free fluoride. With the catalytic subunit a half-maximal effect of either fluorine compound was obtained at 25-50 microM.
2. The inactivation process was instantaneously blocked by the addition of NaF or PMSF at any moment during the incubation of the catalytic subunit with modulator. This fluoride effect was reversible. It did not result from a decreased affinity of modulator for the catalytic subunit. The use of analogues of PMSF showed that the fluorine atom was essential, but structural aspects were also an important determinant.
3. The relative efficiency of fluorine compounds in preventing the inactivation of the catalytic subunit by modulator corresponded to their relative potency as inhibitors of the phosphorylase phosphatase activity, but the latter effect required at least 20-fold higher effector concentrations. Incubation of the catalytic subunit with 10 mM-PMSF or -NaF caused an irreversible inhibition of the enzyme.
4. It is possible to prepare stable complexes of catalytic subunit and modulator, either active or ATPMg-dependent. Both species displayed the same molecular size during gel filtration. The inactive complex could be reactivated by incubation with MgATP and protein kinase FA. NaF and PMSF increased the final extent of re-activation at limiting concentrations of the protein kinase.
PMID: 2848509 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2845943&dopt=AbstractBiochem J 1988 Aug 15;254(1):15-20
Differential effects of fluoride on adenylate cyclase activity and guanine nucleotide regulation of agonist high-affinity receptor binding.
Stadel JM, Crooke ST.
Department of Molecular Pharmacology, Smith Kline and French Laboratories, Philadelphia, PA 19101.
Fluoride ion, presumably an Al3+-F- complex, has been proposed to activate the guanine nucleotide regulatory protein (G-protein) of the visual system, transducin, by associating with GDP at the nucleotide-binding site and thus mimicking the effects of non-hydrolysable GTP analogues [Bigay, Deterre, Pfister & Chabre (1985) FEBS Lett. 191, 181-85]. We have examined this proposed model by using the adenylate cyclase complexes of frog erythrocytes, S49 lymphoma cells and human platelets. Preincubation of plasma membranes from frog erythrocytes and S49 cells with 20 mM-fluoride for 20 min at 30 degrees C strongly stimulated adenylate cyclase activity. In contrast, the preactivated membranes were still able to bind beta-adrenergic agonist with high affinity, as determined by radioligand-binding techniques. Moreover, high-affinity agonist binding in fluoride-treated membranes was fully sensitive to guanine nucleotide, which decreased beta-adrenergic-receptor affinity for agonist. Very similar results were obtained for [3H]prostaglandin E1 binding to S49 membranes pretreated with fluoride. Incubation of human platelet membranes with increasing concentrations of fluoride (1-50 mM) resulted in biphasic regulation of adenylate cyclase activity, with inhibition observed at concentrations greater than 10 mM. Preincubation of platelet membranes with 20 mM-fluoride did not affect agonist high-affinity binding to alpha 2-adrenergic receptors, nor receptor regulation by guanine nucleotide. These results suggest that the model developed from the study of transducin may not be generally applicable to the G-proteins of the adenylate cyclase system.
PMID: 2845943 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2845938&dopt=AbstractBiochem J 1988 Aug 1;253(3):827-33
AlF4- reversibly inhibits 'P'-type cation-transport ATPases, possibly by interacting with the phosphate-binding site of the ATPase.
Missiaen L, Wuytack F, De Smedt H, Vrolix M, Casteels R.
Department of Physiology, Catholic University of Leuven, Belgium.
The only known cellular action of AlF4- is to stimulate the G-proteins. The aim of the present work is to demonstrate that AlF4- also inhibits 'P'-type cation-transport ATPases. NaF plus AlCl3 completely and reversibly inhibits the activity of the purified (Na+ + K+)-ATPase (Na+- and K+-activated ATPase) and of the purified plasmalemmal (Ca2+ + Mg2+)-ATPase (Ca2+-stimulated and Mg2+-dependent ATPase). It partially inhibits the activity of the sarcoplasmic-reticulum (Ca2+ + Mg2+)-ATPase, whereas it does not affect the mitochondrial H+-transporting ATPase. The inhibitory substances are neither F- nor Al3+ but rather fluoroaluminate complexes. Because AlF4- still inhibits the ATPase in the presence of guanosine 5'-[beta-thio]diphosphate, and because guanosine 5'-[beta gamma-imido]triphosphate does not inhibit the ATPase, it is unlikely that the inhibition could be due to the activation of an unknown G-protein. The time course of inhibition and the concentrations of NaF and AlCl3 required for this inhibition differ for the different ATPases. AlF4- inhibits the (Na+ + K+)-ATPase and the plasmalemmal (Ca2+ + Mg2+)-ATPase noncompetitively with respect to ATP and to their respective cationic substrates, Na+ and Ca2+. AlF4- probably binds to the phosphate-binding site of the ATPase, as the Ki for inhibition of the (Na+ + K+)-ATPase and of the plasmalemmal (Ca2+ + Mg2+)-ATPase is shifted in the presence of respectively 5 and 50 mM-Pi to higher concentrations of NaF. Moreover, AlF4- inhibits the K+-activated p-nitrophenylphosphatase of the (Na+ + K+)-ATPase competitively with respect to p-nitrophenyl phosphate. This AlF4- -induced inhibition of 'P'-type cation-transport ATPases warns us against explaining all the effects of AlF4- on intact cells by an activation of G-proteins.
PMID: 2845938 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3131147&dopt=AbstractEur J Pharmacol 1988 Feb 9;146(2-3):279-84
Fluoride stimulates in vitro vascular prostacyclin synthesis: interrelationship of G proteins and protein kinase C.
Jeremy JY, Dandona P.
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, U.K.
The role of G proteins in mediating adrenoceptor-prostacyclin synthesis coupling was investigated using the G protein activator, sodium fluoride. Sodium fluoride (NaF) stimulated in vitro rat aortic prostacyclin (PGI2) synthesis (EC50 = 5 x 10(-3) mol.l-1), an action inhibited completely by the presence of EDTA (10(-2) mol.l-1). The NaF-PGI2 dose-response curve was moved to the left by the presence of adrenaline, phorbol 12,13-dibutyrate (PDBU) and the Ca2+ ionophore A23187 in the incubation media. NaF-stimulated (5 x 10(-3) mol.l-1) PGI2 synthesis was inhibited by the Ca2+ channel blockers, verapamil and nifedipine, the protein kinase C inhibitor, H7, and lanthanum. Prazosin and yohimbine were without effect on NaF action, but partially inhibited adrenaline-potentiated NaF-stimulated PGI2 synthesis. Cyclic adenosine-3',5'-monophosphate (cAMP) and dibutyryl cAMP were without effect on de novo or NaF-, adrenaline-, PDBU- or A23187-stimulated PGI2 synthesis. Since fluoride is known to stimulate adenyl cyclase and phospholipase C, these data suggest that:
(1) NaF stimulates in vitro rat aortic PGI2 synthesis by initiating Ca2+ influx;
(2) this Ca2+ influx is mediated by protein kinase C, probably through G protein activation of phospholipase C and the generation of the protein kinase C activator, diacyl glycerol; and
(3) adenyl cyclase and protein kinase A are not involved in NaF-stimulated PGI2 synthesis by the rat aorta.
PMID: 3131147 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3266960&dopt=AbstractClin Endocrinol (Oxf) 1988 Oct;29(4):437-41
Sodium fluoride stimulates osteocalcin in normal subjects.
Dandona P, Coumar A, Gill DS, Bell J, Thomas M.
Department of Chemical Pathology and Human Metabolism, Royal Free Hospital and School of Medicine, London, UK.
To test whether the administration of sodium fluoride in vivo results in an increase in osteocalcin concentration, we administered sodium fluoride to seven healthy male subjects for a period of 3 weeks. Fasting calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone and osteocalcin were measured prior to, during and 6 weeks after fluoride administration. Plasma calcium, phosphate and alkaline phosphatase and serum 25-hydroxyvitamin D and parathyroid hormone concentrations did not alter. Serum osteocalcin concentrations increased following fluoride administration, and the mean osteocalcin concentration at 3 weeks was significantly higher than the pretreatment mean. Plasma urea and creatinine concentrations did not alter. Six weeks after the cessation of fluoride treatment, the mean serum osteocalcin concentration had returned to the pretreatment baseline. We conclude that fluoride administration in normal subjects over a short period increases serum osteocalcin concentration and probably stimulates osteoblastic activity.
PMID: 3266960 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2963068&dopt=AbstractJ Immunol 1988 Feb 1;140(3):878-84
Sodium fluoride reveals multiple pathways for regulation of surface expression of the C3b/C4b receptor (CR1) on human polymorphonuclear leukocytes.
Okada K, Brown EJ.
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110.
We have examined the effects of NaF on C3b receptor (CR1) expression and function in human polymorphonuclear leukocytes (PMN). Plasma membrane expression of CR1 was determined with a monoclonal antibody (3D9); CR1 function was assessed with erythrocytes bearing C3b (EC3b) or C3b oligomers prepared with avidin and biotin. NaF inhibited in a dose-dependent manner CR1-mediated phagocytosis and NaF inhibited f-met-leu-phe or phorbol dibutyrate-induced increases in CR1 expression, with 50% inhibition at 5 mM NaF. Increased plasma membrane expression of CR3 induced by f-met-leu-phe also was inhibited by NaF. However, increased CR1 and CR3 expression due to incubation at 37 degrees C were unaffected by 10 mM NaF. Incubation of PMN with 10 mM NaF depleted 80% of intracellular adenosine triphosphate (ATP) after 10 min. However, inhibition of CR1 function was unrelated to ATP level, inasmuch as normal increases in CR1 expression and in phagocytosis occurred 20 min after removal of NaF, whereas ATP levels remained below 25% of normal. Strikingly, internalization of soluble oligomeric C3b ligands was unaffected by 10 mM NaF, which completely inhibited phorbol dibutyrate-induced CR1 internalization and EC3b phagocytosis. We conclude that there are two different mechanisms for increasing plasma membrane expression of CR1, one of which is inhibitable by NaF. Moreover, there are two distinct pathways of CR1 internalization which can also be distinguished by their sensitivity to NaF.
PMID: 2963068 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3365517&dopt=AbstractBiol Cell 1988;62(1):33-7
Microcalorimetric studies of hybridoma cells.
Nassberger L, Truedsson L, Monti M.
Research Department 1; University Hospital of Lund, Sweden.
In the present study, overall metabolism has been estimated in hybridoma cells by microcalorimetric measurement. Heat production rate was found to be 30-50 pW/cell at cell concentrations 0.65-4.5 x 10(5)/ml. High cell concentrations (1 x 10(6) cells/ml) caused unstable power-curves with an initial high peak and a rapid declining phase, whereas low cell concentrations (0.6-4.5 x 10(5) cells/ml) produced steady-state power-curves. Oxygen consumption was found to range between 1.5-6.1 x 10(-5) mol 02/cell/min, corresponding to about 80% of the total metabolic activity. The metabolic inhibitors sodium fluoride (50 nM), sodium azide (160 mM) and rotenone (0.1 mM) caused a reduction in overall cell metabolism of 60, 55 and 40% respectively.
PMID: 3365517 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3275545&dopt=AbstractExp Cell Res 1988 Jan;174(1):282-90
Metabolic inhibitors and intermediate filament organization in human fibroblasts.
Klymkowsky MW.
Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309-0347.
A number of metabolic inhibitors including the mRNA transcription inhibitor actinomycin D; the protein synthesis inhibitors emetine, cycloheximide, and puromycin; the energy metabolism inhibitors sodium azide and oligomycin; the amino acid analog L-azetidine-2-carboxylic acid; sodium fluoride; and acrylamide each cause the collapse of vimentin filament organization while leaving microtubule organization apparently unaffected in the human fibroblastic cell line MCH23. The protein kinase inhibitor N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H8) caused a partial collapse of vimentin organization but its effect was more difficult to discern, since it also induced a dramatic change in cellular morphology. Each of these drugs produced a significant inhibition of protein synthesis at concentrations that affected vimentin organization. The mechanisms by which these drugs affect intermediate filament organization are unclear, but our results demonstrate that intermediate filament organization in MCH23 cells is affected by a wide range of drugs and that such drugs cannot be used without great caution as reagents for the study of intermediate filament organization and function.
PMID: 3275545 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2904148&dopt=AbstractProc Natl Acad Sci U S A 1988 Dec;85(23):8958-62
Inhibition of H+-transporting ATPase by formation of a tight nucleoside diphosphate-fluoroaluminate complex at the catalytic site.
Lunardi J, Dupuis A, Garin J, Issartel JP, Michel L, Chabre M, Vignais PV.
Laboratoire de Biochimie, Centre d'Etudes Nucleaires, Grenoble, France.
Inhibition of the mitochondrial and bacterial F1-type ATPases [of ATP phosphohydrolase (H+-transporting), EC 3.6.1.34] by fluoride was found to depend on the presence of aluminum and ADP at the catalytic site(s) of F1-type ATPase. AIF-4 was demonstrated to be the active fluoroaluminate species. The identical pattern of inhibition of F1-type ATPase activity obtained in the presence of ADP and NaF with beryllium, a metal that forms fluoride complexes strictly tetracoordinated, suggests that aluminum acts through a tetrahedral complex. Inhibition of isolated F1-type ATPase by AIF-4 in the presence of ADP cannot be reversed by ADP, ATP, or chelators of aluminum. However, the inhibition of the ATPase activity of the F1 sector in submitochondrial particles caused by AIF-4 and ADP was reversed upon addition of an oxidizable substrate. Uncouplers prevented the reversal of inhibition, suggesting that the protonmotive force generated by respiration was responsible for the relief of inhibition. Because of structural similarities between AIF4- and , AIF4- is postulated to mimic the phosphate group of ATP and form an abortive complex with ADP at the active site(s) of F1-type ATPase.
PMID: 2904148 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3126375&dopt=AbstractLife Sci 1988;42(12):1253-7
The calcium-mobilizing action of low concentrations of sodium fluoride in single fibroblasts.
Kawase T, Ishikawa I, Suzuki A.
Department of Pharmacology, Niigata University School of Dentistry, Japan.
The sensitivity of fibroblasts (L cells) to low concentrations of sodium fluoride (NaF) was examined using the same cell during a series of stimuli. NaF with increasing concentrations up to 1 mM elevated cytosolic free Ca2+ concentrations ([Ca2+]i) in single cells. [Ca2+]i increased within 15 sec of addition of NaF and lowered to basal [Ca2+]i levels quickly. This elevation was observed both in the presence and absence of external Ca2+ and was enhanced by 1 microM Al3+. These results suggest that low concentrations (below 1 mM) of NaF induce Ca2+ release from intracellular Ca2+ stores in single L cells through guanine nucleotide-binding protein (G protein).
PMID: 3126375 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2847698&dopt=AbstractArch Oral Biol 1988;33(5):347-51
Stimulation of mucin release from rat submandibular salivary-gland cells by NaF.
Shahed AR, Allmann DW.
Department of Biochemistry, Indiana University School of Medicine, Indianapolis 46223.
The effect of NaF on cAMP accumulation, cAMP-dependent protein kinase activity (cAMP-dPK) ratios and [14C]-glucosamine-labelled mucin release from these isolated cells was investigated. NaF (0.01-5 mM) increased significantly the cellular cAMP concentration and cAMP-dPK activity ratios in a dose- and time-dependent manner. NaF (5.0 mM) increased [14C]-glucosamine-labelled mucin release in a time-dependent manner. Thus the stimulation of prelabelled mucin secretion by NaF is mediated by an increase in the cAMP concentration, which exerts its effect, at least partly, via the activation of cAMP-dPK activity.
PMID: 2847698 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2446637&dopt=AbstractAm J Emerg Med 1988 Jan;6(1):1-3
Fluoride-induced hyperkalemia: the role of Ca2+-dependent K+ channels.
Cummings CC, McIvor ME.
Philadelphia Heart Institute, Presbyterian University of Pennsylvania Medical Center, Pennsylvania.
Acute fluoride poisoning is associated with sudden cardiac death by an unknown mechanism. Because F- binds to Ca2+ to cause marked hypocalcemia, lowered serum Ca2+ concentrations have been thought to be a major underlying factor in the ventricular irritability of F(-)-toxic patients. However, correction of the hypocalcemia does not prevent sudden death. Paradoxically, while decreasing extracellular Ca2+ levels, in vitro studies have shown F- increases intracellular Ca2+, which is thought to trigger Ca2+-dependent K+ channels and produce a K+ efflux. The K+ efflux may be important clinically, as patients with F- overdose can exhibit hyperkalemia shortly before cardiovascular collapse. In erythrocyte suspensions, we found that propranolol, which increases the sensitivity of the Ca2+-dependent K+ channels, exacerbates the efflux, and quinidine, which blocks the channel, prevents the efflux. In six dogs, 35 mg/kg of sodium fluoride given intravenously produced intractable ventricular fibrillation within 140 minutes. Four dogs given 200 mg of quinidine sulfate with the sodium fluoride developed no ventricular arrhythmias. The data indicate that F--induced hyperkalemia is important in sudden cardiac death following acute fluoride toxicity and that this hyperkalemia is mediated by Ca2+-dependent K+ channels.
PMID: 2446637 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2851472&dopt=AbstractFundam Appl Toxicol 1988 Oct;11(3):373-80
Soman-hydrolyzing and -detoxifying properties of an enzyme from a thermophilic bacterium.
Chettur G, DeFrank JJ, Gallo BJ, Hoskin FC, Mainer S, Robbins FM, Steinmann KE, Walker JE.
IIT Research Institute, Chicago, Illinois 60616.
An enzyme that hydrolyzes soman (1,2,2-trimethylpropyl methylphosphonofluoridate) and two other phosphonofluoridates, but does not hydrolyze DFP (diisopropylphosphorofluoridate), has been partially purified from a rod-shaped spore-forming gram-positive OT (obligate thermophilic) bacterium. The enzyme shows a marked Mn2+ stimulation, and in this and its substrate preference does not resemble the organophosphorus acid anhydrolase (sometimes termed DFPase) found in squid. Like the squid enzyme, it is not inhibited by mipafox (N,N'-diisopropylphosphordiamidofluoridate), is not inactivated by ammonium sulfate, and does hydrolyze the acetylcholinesterase-inhibitory pair of diastereoisomers of soman as well as the relatively noninhibitory pair, thus detoxifying soman. In these three properties the OT enzyme does not resemble the ubiquitous organophosphorus acid anhydrolase often purified from mammalian and bacterial sources by cold ethanol fractionation. Thus this phosphono-specific OT enzyme may have a natural substrate and a physiological role distinct from other organophosphorus acid anhydrolases.
PMID: 2851472 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3408711&dopt=AbstractBiochemistry 1988 May 17;27(10):3555-9
- Erratum in:
- Biochemistry 1989 Apr 18;28(8):3628
Stabilization of microtubules by inorganic phosphate and its structural analogues, the fluoride complexes of aluminum and beryllium.
Carlier MF, Didry D, Melki R, Chabre M, Pantaloni D.
Laboratoire d'Enzymologie, CNRS, 91198 Gif-sur-Yvette, France.
In order to elucidate how the elementary reactions of GTP cleavage and subsequent inorganic phosphate (Pi) release, which accompany microtubule assembly, regulate microtubule dynamics, the effect of Pi and of its structural analogues AlF4- and BeF3- on the stability of GDP-microtubules has been investigated. Inorganic phosphate binds to microtubules with a low affinity (KD = 25 mM) and slows down the rate of GDP-subunit dissociation by about 2 orders of magnitude. AlF4- and BeF3- exhibit phosphate-like effects with 1000-fold higher affinity. Evidence has been obtained for direct binding of BeF3- to microtubules with a stoichiometry of 1 mol of BeF3- per mole of GDP-subunit and an equilibrium dissociation constant of 12-15 microM. AlF4- and Pi compete for this site. Phosphate analogues abolish oscillatory polymerization kinetics and slow down microtubule turnover at steady state. In view of these results, we propose that Pi and its structural analogues bind to the site of the gamma-phosphate of GTP in the E site and reconstitute a GDP-Pi-microtubule, from which tubulin subunits dissociate very slowly. We therefore understand that, following GTP cleavage on microtubules, Pi release in the medium is accompanied by a structural change resulting in a large destabilization of the polymer. A cap of slowly dissociating GDP-Pi-subunits prevents depolymerization of the microtubule GDP-core at steady state. The similarity with the actin system [Carlier, M.-F., & Pantaloni, D. (1988) J. Biol. Chem. 263, 817-825] is underlined.
PMID: 3408711 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3182855&dopt=AbstractJ Biol Chem 1988 Nov 25;263(33):17429-36
Probing the mechanism of ATP hydrolysis on F-actin using vanadate and the structural analogs of phosphate BeF-3 and A1F-4.
Combeau C, Carlier MF.
Laboratoire d'Enzymologie, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
The binding of phosphate analogs to F-ADP-actin filaments and their effect on the dynamics of the polymer have been investigated. Orthovanadate binds to F-actin with the same affinity as phosphate and, at low saturation levels, stabilizes the filament structure in a Pi-like fashion; at higher concentration, it promotes destabilization of the filament. BeF-3 and A1F-4 bind to F-ADP-actin in competition with Pi, with a stoichiometry of 1 mol/mol of F-actin subunit and an affinity 3 orders of magnitude higher than Pi (KD = 2 and 25 microM for BeF-3 and A1F-4, respectively). BeF-3 and A1F-4 mimic Pi in stabilizing F-actin and slow down the rate of actin dissociation from filaments 150-fold. Only 1% of F-ADP-BeF3 subunits provide extensive stabilization of the filament. A quantitative analysis of the stabilization by BeF-3 is proposed. While Pi appears in rapid equilibrium with F-ADP-actin, BeF-3 binds to and dissociates from F-ADP-actin at very slow rates (k+ = 4 M-1 S-1; k = 8.10(-6) S-1). In addition, although functionally similar to the reconstituted F-ADP-Pi species, F-ADP-BeF3 has a different conformation as indicated by the 17% quenching of pyrenyl fluorescence linked to BeF-3 binding. We suggest that BeF-3 may be a good analog of the transition state F-ADP-P* and that Pi release following cleavage of ATP on F-actin might be rate-limited by the isomerization of F-ADP-P*.
PMID: 3182855 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3215277&dopt=AbstractEur J Pharmacol 1988 Aug 9;153(1):123-9
Modulation of the accumulation of inositol phosphates and the mobilization of calcium in aortic myocytes.
Berta P, Phaneuf S, Travo P, Cavadore JC.
Centre de Recherches de Biochimie Macromoleculaire, LP 8402/C.N.R.S., I.N.S.E.R.M./U 249, Faculte de Medecine, Montpellier, France.
In vascular smooth muscle cells the phorbol ester, 12-O-tetradecanoyl phorbol 13-acetate (TPA), a potent activator of C-kinase, inhibited the accumulation of inositol phosphates and the mobilization of calcium produced by several agonists. In the same way, TPA inhibited the fluoride-induced activation of phosphoinositide metabolism. These results suggest a C-kinase action at a post-receptor level. Moreover, the fluoride-induced accumulation of inositol phosphates shows the presence of one or more guanine nucleotide-binding proteins (G-proteins) in the regulation of receptor-phospholipase C coupling. This was confirmed by the use of N-ethylmaleimide and pertussis toxin. These results support the view that, in addition to the induction of sustained contractions, C-kinase can activate negative feedback mechanisms in aortic myocytes.
PMID: 3215277 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3230598&dopt=AbstractJ Toxicol Clin Toxicol 1988;26(7):467-76
Chronic fluoride toxicity: a scanning electron microscopic study of duodenal mucosa.
Susheela AK, Das TK.
Department of Anatomy, All India Institute of Medical Sciences, New Delhi.
The effects of chronic fluoride toxicity on duodenal mucosa of rabbits were investigated using scanning electronmicroscope on materials obtained from rabbits subjected to oral administration of sodium fluoride at the dose of 10 mg/kg body weight per day for a period of 24 months. Significant morphological abnormalities were observed in the mucosa of all the fluoride treated animals [n = 9] when compared to that of control rabbits. The surface of the microvilli of duodenal epithelium revealed a "cracked-clay" appearance in fluoride treated rabbits. Besides, abrasion on the villus surface due to epithelial cell degeneration was also noticed. Mucus probably coating the degenerated cells formed strands over the villi in fluoride treated animals.
PMID: 3230598 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3126278&dopt=AbstractJ Nucl Med 1988 Mar;29(3):363-9
Metabolites of 6-[18F]fluoro-L-dopa in human blood.
Firnau G, Sood S, Chirakal R, Nahmias C, Garnett ES.
McMaster University Medical Centre, Chedoke-McMaster Hospitals, Section of Radiology, Hamilton, Ontario, Canada.
The metabolites of 6-[18F]fluoro-L-dopa in the blood plasma of healthy humans have been identified as 3-O-sulfato-6[18F]fluoro-L-dopa, 3-O-methyl-6-[18F]fluoro-L-dopa, 6-[18F] fluorodopamine, and 6-[18F]fluorohomovanillic acid. The time course of these metabolites was followed up to 2 hr. The findings have implications for the use of 6-[18F]fluoro-L-dopa as tracer for cerebral dopamine metabolism. Despite the variety of metabolites in the peripheral blood there are only two 18F-carrying compounds, 6-[18F]fluoro-L-dopa and 3-O-methyl-6-[18F]fluoro-L-dopa, that can cross the blood-brain barrier. After 1 hr, the plasma concentration of 3-O-methyl-6-[18F]fluoro-L-dopa reaches approximately 20% that of 6-[18F]fluoro-L-dopa but the mean concentration of the O-methylated metabolite over the same interval is less than 5% that of 6-[18F]-fluoro-L-dopa.
PMID: 3126278 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2845690&dopt=AbstractActa Endocrinol (Copenh) 1988 Oct;119(2):174-80
The role of zinc status in altered cardiac adenylate cyclase activity in diabetic rats.
Mooradian AD, Morley JE, Scarpace PJ.
Geriatric Research, Education and Clinical Center, V.A. Medical Center, Sepulveda, CA.
Zinc deficiency and altered myocardial adenylate cyclase activity commonly occur in diabetes. To determine whether the zinc intake of the animal can account for the altered beta-adrenergic receptor activity in the diabetic heart, we determined the beta-adrenergic receptor number and isoproterenol-, NaF- and forskolin-stimulated adenylate cyclase activity in diabetic and control rats maintained on low, normal and high zinc diets for 3 weeks. Scatchard analysis of [125I]iodocyanopindolol binding to control heart membrane preparations revealed a binding capacity of 17.3 +/- 1.3 fmol/mg protein with a Kd of 35 +/- 1.0 pmol/l. Neither the diabetic state nor the zinc status altered these binding parameters. The isoproterenol-stimulated adenylate cyclase activity was significantly lower in diabetic rats on low zinc diets compared with controls. The NaF- (65.1 +/- 5.4 vs 60.8 +/- 6.4 pmol cAMP.mg protein-1.min-1) and forskolin-stimulated adenylate cyclase activities (161 +/- 9.3 vs 154 +/- 21.2 pmol cAMP.mg protein-1. min-1) were not significantly altered in diabetic rats. Low dietary zinc intake compared with high zinc diet significantly increased NaF- and forskolin-stimulated adenylate cyclase activity both in diabetic rats and controls. The effect of dietary zinc content on isoproterenol-stimulated adenylate cyclase was significant in control rats only. Thus zinc intake appears to be an important determinant of cardiac adenylate cyclase activity level. Additional factors peculiar to the diabetic state are involved in the modulation of beta-adrenergic responsiveness of the diabetic heart.
PMID: 2845690 [PubMed - indexed for MEDLINE]
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