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1992 Fluoride Abstracts. Part 1.

Abstracts for the following years:
Part 1 - mainly biochemistry and physiology (brain, hormonal, G-proteins, etc.)
Part 2 ("b") - all other

2007

2007-b

2004

2004-b

2001

2001-b

1998

1998-b

1995

1995-b

1992

1992-b

1989

1989-b

1986

1986-b

1983

1982

1976 -
1977
1970 -
1971

2006

2006-b

2003

2003-b

2000

2000-b

1997

1997-b

1994

1994-b

1991

1991-b

1988

1988-b

1985

1985-b

1981

1980

1974 -
1975
1968 -
1969

2005

2005-b

2005-b continued

2002

2002-b

1999

1999-b

1996

1996-b

1993

1993-b

1990

1990 -b

1987

1987-b

1984

1984-b

1979

1978

1972 -
1973
Up to
1967

 

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1362805&dopt=Abstract

Neurosci Lett 1992 Dec 7;147(2):143-6

Astrocyte
glutamate uptake during chemical hypoxia in vitro.

Swanson RA.

Department of Neurology, Veterans Affairs Medical Center, San Francisco, CA 94121.

Glutamate uptake was measured in primary rat cortical astrocyte cultures exposed to sodium azide, 2,4-dinitrophenol, or antimycin A to assess the ability of astrocytes to function under hypoxic conditions. Uptake was maintained at 54-63% of control values despite maximal inhibition of oxidative ATP production. In contrast, the glycolytic inhibitor sodium fluoride (20 mM) reduced glutamate uptake by more than 95% when glucose was the only available substrate. These data suggest that glutamate uptake is largely maintained during hypoxia provided glucose remains available. Astrocyte glutamate uptake may aid neuronal survival during conditions such as incomplete ischemia where oxygen but not glucose is depleted.
PMID: 1362805 [PubMed - indexed for MEDLINE]
[Note from FAN:
Definition of astrocyte - one of the large neuroglia cells of nervous tissues.
Ref: Stedman's Concise Medical Dictionary for the Health Professions. Illustrated 4th Edition. 2001.]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1473206&dopt=Abstract

Zhonghua Bing Li Xue Za Zhi 1992 Aug;21(4):218-20
[The effect of fluorine on the developing human brain]

[Article in Chinese]

Du L.

Department of Pathology, Guiyang Medical College.

Fifteen therapeutically aborted fetuses at the 5th-8th gestation month from the endemic fluorosis area were compared with those from the non-endemic area. Stereological study of the brains showed that the numerical density of volume of the neurons and the undifferentiated neuroblasts as well as the nucleus-cytoplasm ratio of the neurons were increased. The mean volume of the neurons was reduced. The numerical density of volume, the volume density and the surface density of the mitochondria were significantly reduced. The results showed that chronic fluorosis in the course of intrauterine fetal life may produce certain harmful effects on the developing brain of the fetus.

PMID: 1473206 [PubMed - indexed for MEDLINE]

Fluoride 1992; 25(2):77-84

Studies on alterations in brain lipid metabolism following experimental fluorosis

A Shashi

Department of Zoology, Punjabi University, Patala 147002, India

Summary: The neurotoxic effect of fluoride on lipid content of brain was assessed in rabbits during experimental fluorosis. Sodium fluoride at 5, 10, 20 and 50 mg/kg body weight/day was injected subcutaneously for 100 days into 60 rabbits of both sexes. The control animals were given 1 cc distilled water/kg body weight/day for the same period. Biochemical studies showed hyperlipidemia, hyperphospholipidemia, and hypertriglyceridemia in the brain of treated animals of both sexes. The maximum increase in total lipids, phospholipids and triglycerides of brain occurred in animals treated with 50 mg NaF/kg. In male rabbits, the cholesterol content of brain rose suddenly (p<0.001) in the 5 mg fluoride group, followed by gradual decline in 10, 20 and 50 mg fluoride groups. In females, the cholesterol level rose (p<0.001) in animals of the 5, 10 and 20 mg fluoride groups and fell suddenly in the 50 mg fluoride group. Fluoride exerts an inhibitory effect on the free fatty acids in brain of both sexes. The relevance of these results in experimental fluorosis is discussed.

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1362805&dopt=Abstract

Neurosci Lett 1992 Dec 7;147(2):143-6

Astrocyte
glutamate uptake during chemical hypoxia in vitro.


Swanson RA.

Department of Neurology, Veterans Affairs Medical Center, San Francisco, CA 94121.

Glutamate uptake was measured in primary rat cortical astrocyte cultures exposed to sodium azide, 2,4-dinitrophenol, or antimycin A to assess the ability of astrocytes to function under hypoxic conditions. Uptake was maintained at 54-63% of control values despite maximal inhibition of oxidative ATP production. In contrast, the glycolytic inhibitor sodium fluoride (20 mM) reduced glutamate uptake by more than 95% when glucose was the only available substrate. These data suggest that glutamate uptake is largely maintained during hypoxia provided glucose remains available. Astrocyte glutamate uptake may aid neuronal survival during conditions such as incomplete ischemia where oxygen but not glucose is depleted.

PMID: 1362805 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1471154&dopt=Abstract

Toxicol Appl Pharmacol 1992 Dec;117(2):218-25

Local application of neuropathic organophosphorus compounds to hen sciatic nerve: inhibition of neuropathy target esterase and peripheral neurological impairments.


Carrera V, Barril J, Mauricio M, Pellin M, Vilanova E.

Department of Neurochemistry, University of Alicante, Spain.

Diisopropyl phosphorofluoridate (DFP), mipafox, cresylsaligenyl phosphate, and phenylsaligenyl phosphate were applied to a 1.5-cm segment of the common trunk of the sciatic nerve in adult hens. At doses of 18-182 micrograms mipafox and 9-110 micrograms DFP, inhibition of neuropathy target esterase (NTE) for the treated segment was over 80%, whereas for the adjacent distal and proximal segments inhibition was under 40%, 15 min after application. NTE was not affected in the peripheral distal terminations arising from the common sciatic nerve (peroneal branches), contralateral sciatic nerve, brain, and spinal cord. A 24-hr study suggested a displacement of the activity-free region toward more distal segments of the nerve. All animals treated with 55 and 110 micrograms DFP or 110 micrograms mipafox lost a characteristic avian retraction reflex in the treated leg 9-15 days after dosing, suggesting peripheral neurological alterations. Only hens dosed at the maximum dose in both extremities presented alterations in motility (Grade 1 or 2 on a 0-8 scale), suggesting no significant central nervous system alterations. Electron microscopy of peroneal branches showed axon swelling and accumulation of smooth endoplasmic reticulum similar to animals dosed systemically (s.c.) with 1-2 mg/kg DFP. The branches also contained granular and electron-dense materials, as well as some intraaxonal and intramyelinic vacuolization. Clinical effects were not observed in animals protected with a 30 mg/kg (s.c.) dose of phenylmethanesulphonyl fluoride. It is concluded that the peripheral neurological effects of local dosing correlate with the specific modification of NTE in a segment of sciatic nerve and that the axon is a more likely target than the perikaryon or nerve terminal in the triggering mechanism of this axonopathy.

PMID: 1471154 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1361027&dopt=Abstract

Neurochem Res 1992 Nov;17(11):1133-41

Guanine nucleotide- and muscarinic agonist-dependent phosphoinositide metabolism in synaptoneurosomes from cerebral cortex of immature rats.


Candura SM, Castoldi AF, Manzo L, Costa LG.

Department of Environmental Health, University of Washington, Seattle 98195.

Guanine nucleotide-, neurotransmitter-, and fluoride-stimulated accumulation of [3H]inositol phosphates ([3H]InsPs) was measured in [3H]inositol-labeled synaptoneurosomes from cerebral cortex of immature (7-day-old) and adult rats, in order to clarify the role of GTP-binding proteins (G-proteins) in modulating phosphoinositide (PtdIns) metabolism during brain development. GTP(S) [Guanosine 5'-O-(3-thio)triphosphate] time- and concentration-dependently stimulated PtdIns hydrolysis. Its effect was potentiated by full (carbachol, metacholine) and partial (oxotremorine) cholinergic agonists through activation of muscarinic receptors. The presence of deoxycholate was required to demonstrate agonist potentiation of the guanine nucleotide effect. The response to GTP(S) was higher in adult than in immature rats, while the effect of cholinergic agonists was similar at the two ages examined. At both ages, histamine potentiated the effect of GTP(S), while norepinephrine was ineffective. At both ages, guanosine 5'-O-(2-thio)diphosphate [GDP(S)] and pertussis toxin significantly decreased GTP(S)-induced [3H]InsPs formation. The phorbol ester phorbol 12-myristate 13-acetate (PMA), on the other hand, did not inhibit the guanine nucleotide response in synaptoneurosomes from immature rats. NaF mimicked the action of GTP(S) in stimulating PtdIns hydrolysis. Its effect was not affected by carbachol and was highly synergistic with that of AlCl3, according to the concept that fluoroaluminate (AlF4-) is the active stimulatory species. No quantitative differences were found in the response to these salts between immature and adult animals. These results provide evidence that, in both the immature and adult rat brain, neuroreceptor activation is coupled to PtdIns hydrolysis through modulatory G-proteins.

PMID: 1361027 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1573399&dopt=Abstract

J Neurochem 1992 Jun;58(6):2200-6

Chronic lithium treatment impairs phosphatidylinositol hydrolysis in membranes from rat brain regions.


Song L, Jope RS.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.

Membranes prepared from rat brain regions were used to measure the receptor-coupled and/or guanine nucleotide-binding protein (G protein)-mediated hydrolysis of exogenous [3H]phosphatidylinositol ([3H]PI). Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and NaF (in the presence of AlCl3) caused concentration-dependent stimulations of [3H]PI hydrolysis, supporting the conclusion that G proteins mediating [3H]PI hydrolysis can be activated in this preparation. Neither of these responses was altered by in vitro incubation with 8 mM LiCl, but both were reduced in hippocampal, striatal, and cortical membranes from rats that had been treated with lithium for 4 weeks compared with controls. Two cholinergic agonists, carbachol and pilocarpine, induced no hydrolysis of [3H]PI unless GTP gamma S was also present, in which case each equally stimulated [3H]PI hydrolysis above that obtained with GTP gamma S alone. In the presence of GTP gamma S several excitatory amino acid agonists stimulated [3H]PI hydrolysis to an extent similar to that of carbachol. After chronic lithium treatment, [3H]PI hydrolysis stimulated by carbachol was significantly attenuated, but the response to quisqualate was unaffected. Therefore, lithium added in vitro does not have an effect on cholinergic receptor- or G protein-mediated [3H]PI hydrolysis, but each of these is reduced by chronic lithium treatment. Because exogenous [3H]PI was provided as the substrate, it is evident that the inhibitory effect of chronic lithium treatment cannot be due to substrate depletion. Impaired function of G proteins appears to be the most likely mechanism accounting for attenuated [3H]PI hydrolysis after chronic administration of lithium.

PMID: 1573399 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1548475&dopt=Abstract

J Neurochem 1992 Apr;58(4):1409-19

Adenylyl cyclase activity in postmortem human brain: evidence of altered G protein mediation in Alzheimer's disease.


Cowburn RF, O'Neill C, Ravid R, Alafuzoff I, Winblad B, Fowler CJ.

Department of Geriatric Medicine, Karolinska Institute, Huddinge, Sweden.

The effects of agonal status, postmortem delay, and age on human brain adenylyl cyclase activity were determined in membrane preparations of frontal cortex from a series of 18 nondemented subjects who had died with no history of neurological or psychiatric disease. Basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were not significantly reduced over an interval from death to postmortem of between 3 and 37 h and were also not significantly different between individuals dying with a long terminal phase of an illness and those dying suddenly. Basal and aluminum fluoride-stimulated enzyme activities showed a negative correlation with increasing age of the individual. In subsequent experiments, basal and guanosine 5'-O-(3-thiotriphosphate)-, aluminum fluoride-, and forskolin-stimulated enzyme activities were compared in five brain regions from a series of eight Alzheimer's disease and seven matched nondemented control subjects. No significant differences were observed between the groups for either basal activity or activities in response to forskolin stimulation of the catalytic subunit of the enzyme. In contrast, enzyme activities in response to stimulation with guanosine 5'-O-(3-thiotriphosphate) and aluminum fluoride were significantly reduced in preparations of neocortex and cerebellum from the Alzheimer's disease cases compared with the nondemented controls. Lower guanosine 5'-O-(3-thiotriphosphate)-, but not aluminum fluoride-, stimulated activity was also observed in preparations of frontal cortex from a group of four disease controls compared with nondemented control values. The disease control group, which contained Parkinson's disease and progressive supranuclear palsy patients, showed increased forskolin-stimulated activity compared with both the nondemented control and the Alzheimer's disease groups. These findings indicate a widespread impairment of G protein-stimulated adenylyl cyclase activity in Alzheimer's disease brain, which occurs in the absence of altered enzyme catalytic activity and which is unlikely to be the result of non-disease-related factors associated with the nature of terminal illness of individuals.

PMID: 1548475 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1508395&dopt=Abstract

Neurosci Lett 1992 Jul 6;141(1):16-20

Preservation of Gi-protein inhibited adenylyl cyclase activity in the brains of patients with Alzheimer's disease.


Cowburn RF, O'Neill C, Ravid R, Winblad B, Fowler CJ.

Department of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.

The coupling of inhibitory guanine nucleotide binding (Gi) proteins to the adenylyl cyclase signal transduction complex was compared in 4 brain regions from a series of Alzheimer's disease and matched control subjects by measuring the inhibition of membrane enzyme activities in response to guanosine 5'-[beta gamma-imido]diphosphate (Gpp[NH]p) and aluminium fluoride (AlF4-). Basal adenylyl cyclase activities were significantly lower in preparations of angular gyrus and frontal and temporal cortices, but not cerebellum, from the Alzheimer's disease cases compared to controls. Gpp[NH]p and AlF4- gave significant inhibitions of adenylyl cyclase activity in all brain regions. The magnitude of these inhibitions, when corrected for altered basal activities, were similar for the Alzheimer's disease and control cases. These results indicate that there is no impairment of Gi-protein mediated inhibition of adenylyl cyclase activity in Alzheimer's disease brain.

PMID: 1508395 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1532197&dopt=Abstract

J Neurochem 1992 Apr;58(4):1547-54

Potentiation of N-methyl-D-aspartate-stimulated dopamine release from rat brain slices by aluminum fluoride and carbachol.


Woodward JJ, Harms J.

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.

N-Methyl-D-aspartate (NMDA) stimulated the release of endogenous dopamine from striatal slices prepared from adult Sprague-Dawley rats. A mixture of sodium fluoride and aluminum chloride (AlF4-) added to the slices significantly potentiated the NMDA-stimulated release of dopamine in a concentration- and time-dependent manner. The AlF4- mixture had no effect on the nonstimulated basal efflux of dopamine, and no increases in NMDA-stimulated release were observed when NaF was replaced with NaCl. Similarly, AlCl3 or a mixture of NaCl and AlCl3 had no effect on NMDA-stimulated release. The AlF(4-)-induced increase in NMDA-stimulated dopamine release was totally blocked by magnesium or the selective NMDA glycine antagonist 7-chlorokynurenic acid. Striatal slices depolarized with KCl (15 mM) also released dopamine and this release was similarly potentiated by AlF4-. However, KCl-stimulated dopamine release from striatal synaptosomes was not potentiated by concentrations of AlF4- that greatly increased release from striatal slices. NMDA did not stimulate the release of dopamine from striatal synaptosomes in the absence or presence of aluminum fluoride. Modulators of adenylate cyclase (forskolin) and protein kinase C (phorbol esters) did not enhance NMDA-stimulated dopamine release. The protein kinase C inhibitor H-7 also did not reduce the potentiating effects of AlF4-. The mixed cholinergic agonist carbachol and the calcium ionophore A23187 mimicked the AlF4- effect although the increase in NMDA-stimulated dopamine release produced by these agents was less than that seen with AlF4-.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 1532197 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1343587&dopt=Abstract

Acta Physiol Pharmacol Ther Latinoam 1992;42(3):183-96

Fluoride
and phosphatidylserine induced inhibition of cytosolic insulin-degrading activity.


Udrisar DP, Wanderley MI.

Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil.

Cytosol (C) (100,000 x g/60 min, supernatant) from liver, brain and testis (Wistar male rats) are shown to contain insulin degrading activity (C-IDA). The regulation of C-IDA in these fractions by ligands that activate G protein and PKC were examined C-IDA from liver, brain and testis was inhibited 76%; 64% and 50% by 50 mM F- respectively. Chromatography of C fraction from liver on Sephadex G-50 in presence of 1 M (NH4)2SO4 and 20% (v/v) glycerol (experimental condition to remove guanine nucleotides from G proteins) decreased in about 3-fold aluminum fluoride effect on C-IDA. Mg++ (from 5mM to 10 mM) enhanced fluoride effects by inhibiting fully C-IDA. Phosphatidylserine in presence of ATP completely inhibited C-IDA; this inhibition was 31.3% mediated by a phosphorylation reaction. It is concluded that cytosol from different tissues contain proteins capable to associate ligands as aluminum fluoride and PS to regulate C-IDA. It is proposed a mechanism of protein-protein interaction to modulate C-IDA.

PMID: 1343587 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1331919&dopt=Abstract

Neurotoxicology 1992 Summer;13(2):389-400

Seizures selectively impair agonist-stimulated phosphoinositide hydrolysis without affecting protein kinase C activity in rat brain.


Jope RS, Kolasa K, Song L, Ormandy GC.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama, Birmingham 35294.

The influence of seizures on phosphoinositide hydrolysis and protein kinase C activity was measured in rat hippocampus and cerebral cortex, primarily using a model in which generalized convulsive status epilepticus was induced by administration of LiCl (3 mmole/kg) 20 hr prior to pilocarpine (30 mg/kg). A short (5 min) period of seizures reduced phosphoinositide hydrolysis in hippocampal slices stimulated by norepinephrine or ibotenate, but did not alter the responses to carbachol, 50 mM K+, or NaF. Induction of seizures with diisopropylfluorophosphate caused a similar reduction in the response to norepinephrine without altering carbachol-stimulated phosphoinositide hydrolysis. The inhibition of norepinephrine-stimulated phosphoinositide hydrolysis after seizures generated by lithium plus pilocarpine administration was apparently not due to inhibitory influences of quisqualate or activation of protein kinase C since both of these treatments caused similar inhibitions in slices from control and treated rats. Seizures induced by lithium plus pilocarpine or by kainate did not alter the activity of protein kinase C or the distribution of protein kinase C between membrane and cytosolic fractions. Thus, seizures cause a neurotransmitter-selective impairment of phosphoinositide hydrolysis, and this response may play a role in the severity or duration of seizure activity.

PMID: 1331919 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1324092&dopt=Abstract

Res 1992 Jun 26;583(1-2):155-60

Beta-adrenergic receptor activity of cerebral microvessels in experimental diabetes mellitus.


Mooradian AD, Scarpace PJ.

St. Louis DVA Medical Center, MO.

The effect of diabetes mellitus on beta-adrenergic receptor number (B(max)), receptor-cyclase coupling and adenylate cyclase (AC) activity was determined in cerebral microvessels isolated from control and streptozotocin induced diabetic rats after 5 weeks of induction of diabetes. Scatchard analysis of [125I]iodocyanopindolol (ICYP) binding indicated that the B(max) (fmol/mg) in diabetic rat cerebral microvessels (63.8 +/- 4.8) (mean +/- S.E.M.) was not significantly different from the B(max) in control rats (56.5 +/- 6.9). Isoproterenol competition of [125I]ICYP binding sites indicated that the percentage of beta-receptors expressing high affinity binding was 53.9 +/- 0.45% in control rats and 47.5 +/- 2.3% in diabetic rats. The total isoproterenol-stimulated AC activity (pmol cAMP/mg) in diabetic rats (76.7 +/- 6.1) was significantly lower than that in control rats (118.4 +/- 11.2) (P less than 0.01). However, the net isoproterenol-stimulated AC activity (i.e. total minus GTP-stimulated AC activity) was not altered in diabetes. The net sodium fluoride (NaF) stimulated AC activity in diabetic rats (109.5 +/- 11.4) was significantly lower than the control rats (154.3 +/- 16.3) (P less than 0.05). It is concluded that diabetes mellitus in rats is associated with reduced post receptor activation of adenylate cyclase in cerebral microvessels while the beta-adrenergic receptor density, affinity and receptor-cyclase coupling are not significantly altered.

PMID: 1324092 [PubMed - indexed for MEDLINE]


Fiziologicheskii Zhurnal 1992; 38(1):42-6
Sodium fluoride influence upon energy and protein liver metabolism after its experimental ishemia

IM Tyrtyshnikov and VP Pedik

Reprints: IM Tyrtyshnikov, Ministry of Public Health, Institute of Medical Stomatology, Poltava, Ukraine

The experimental study of 88 white rats has stated that peroral introduction of sodium fluoride at a rate of 1.2 mg per 100 g of mass in animals during 3 month period is followed by development of fluoride intoxication, that causes considerable decrease of liver resistance to ishemia and more vivid disturbances of its energy and protein metabolism. The activity of the restoration plastic process after ishemia decreases. A conclusion is drawn that fluoride can influence the seriousness of illness, ishemia underlying it.

Complimentary Medical Research 1992; 6:111-113
Effects of fluoride on immune system function

SLM Gibson

Research Physician, Glascow Homeopathic Hospital, 1000 Great Western Road, Glascow G12 0NR, Scotland

The fluoridation of public water supplies was introduced over 40 years ago in the belief that it was beneficial to teeth. More recent evidence, however, reveals no lasting benefit and suggests that fluoride may be harmful to many physiological systems. T
he present study investigates effects of fluoride on the immune system. The results show that concentrations of 0.5, 1.0, 2.0 and 20.0 ug/ml significantly inhibit the ability of white blood cells (leucocytes) to migrate after incubation for 3 hours at 37¼C. The concentrations include those used in public water supplies and the ability of leucocytes to migrate was significantly impaired even at the lowest concentrtions. All the concentrations are lower than those used in fluoridated toothpastes, topical gels and mouth rinses, which are often swallowed, particularly by young children. In this study the white blood cells were eposed to the various concentrations for 3 hours. Where water fluoridation is undertaken, exposures are continuous and life-long, reported values for plasma fluoride ranging from 0.7 to 2.4 ug/ml. While some of the blood samples used in this study showed little or no inhibition at those low concentrations, some were obviously affected, the mean effect being significant at all concentrations. The author concludes: "A section of the population may therefore be at risk of compromised immune system function from water fluoridation schemes. All recent large-scale surveys have shown minimal benefits to teeth from fluoridation programmes. On the other hand, chronic exposure to fluoride at 1 ug/ml could have a long-term detrimental effect on the general health of the population. Over the past 20 to 30 years there has been a substantial and unexplained rise in a number of conditions such as allergy, auto-immune diseases and the post viral fatigue syndrome. The common factor in these conditions is an alteration in the efficiency of the immune system."

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1392294&dopt=Abstract

Bull Environ Contam Toxicol 1992 Jul;49(1):44-50

No Abstract available

Elevated cholinesterase activity and increased urinary excretion of inorganic fluorides in the workers producing fluorine-containing plastic (polytetrafluoroethylene).


Xu B, Zhang J, Mao G, Yang G, Chen A, Aoyama K, Matsushita T, Ueda A.

Department of Industrial Health and Occupational Disease, Faculty of Preventive Medicine, China Medical University, Shenyang.

PMID: 1392294 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1344226&dopt=Abstract

Indian J Pathol Microbiol 1992 Oct;35(4):351-6

Testicular proteins and DNA in experimental fluorosis.

Shashi, Kaur D.

Department of Zoology, Punjabi University, Patiala, India.

Experimental fluorosis was induced in young male albino rabbits by exposing them to 0, 5, 10, 20 and 50 mg of NaF via subcutaneous injections for a period of 3-1/2 months. The testicular structural, nuclear and total proteins were significantly depleted in all test groups of animals as compared to the control. There was a significant (p < 0.001) reduction in the testicular DNA after drug administration. The relevance of these results in experimental fluorosis has been discussed.

PMID: 1344226 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1360374&dopt=Abstract

Comp Biochem Physiol C 1992 Sep;103(1):31-4

The effect of high fluoride intake on tissue trace elements and histology of testicular tubules in the rat.

Krasowska A, Wlostowski T.

Institute of Biology, Bialystok Branch of Warsaw University, Poland.

1. Male Wistar rats were exposed to fluoride (F) at concentrations of 100- and 200 ppm in their drinking water for 6- and 16 weeks.
2. The high F intake caused several-fold increase in the F concentrations in the testes and bone as compared with control rats, both after the 6- and 16 wk exposure; the bone F, but not testicular F, appeared to increase with dose and time.
3. F exposure (100- and 200 ppm) decreased significantly the concentrations of zinc (Zn) in the testes, plasma, liver and kidneys particularly in the 16 wk groups; in the bone Zn tended to increase, however.
4. The iron concentrations of the testes and plasma were not affected by F, whereas those of the liver, kidneys and bone appeared to increase under the influence of F.
5. The concentrations of copper and manganese in the testes, liver and kidneys were not changed by F exposure.
6. Fifty percent of the 100- and 200 ppm F rats after 16 weeks exhibited histopathologic changes in the germinal epithelium of the testes, which resembled those in Zn-deficient rats.
7. The data suggest that a deprivation of testicular Zn due to a high F intake may be directly responsible for the injury of testicular tubules.

PMID: 1360374 [PubMed - indexed for MEDLINE]


Fluoride 1992; 25(2):71-76

Reversible fluoride induced fertility impairment in male mice

NJ Chinoy * and E Sequeira

* Department of Zoology, University School of Sciences, Gujarat University, Ahmedabad, Gujarat, India

Summary: Sodium fluoride (NaF) fed to adult male albino mice at a dose of 10 mg and 20 mg/kg body weight, caused a significant decrease in sperm county and motility. Scanning electron microscopy and silver nitrte staining showed large numbers of deflagellated spermatozoa, with acrosomal, midpiece and tail abnormalities. The treatment caused loss of fertility rate when normal cycling female mice were mated with treated males. Withdrawal of treatment for a period of 2 months resulted in a significant recovery in sperm count and sperm motility as well as fertility rate.


Fluoride 1992; 25(3):149-154

Biochemical effects of fluoride on lipid metabolism in the reproductive organs of male rabbits

A Shashi

Department of Zoology, Punjabi University, Patala 147002, India

Summary: The effect of fluoride on testicular lipid metabolism was assessed in male albino rabbits in experimental fluorosis. Fifty male albino rabbits were administered sodium fluoride (5, 10, 20, and 50 mg/kg body weight/day) subcutaneously for 100 days. The control animals were given 1 cc distilled water/kg body weight over the same period. Compared with controls, the experimental animals, especially those given 50 mg NaF/day/kg of body weight, showed abnormal accumulation of lipids in testes. Hyperphospholipidemia, hypertriglyceridemia, and hypercholesterolemia in testes indicate enhanced lipid biosynthesis in response to fluoride toxicosis. A progressive significant (p<0.001) increase in amount of free fatty acids was observed in testes of fluoridated animals. The increase of concentrtion of all lipid classes except free fatty acids in testes was directly correlated with the increase in dosage of fluoride administered.


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1626048&dopt=Abstract

Radiat Res 1992 Jul;131(1):47-52

Effect of fluoride on inhibition of plasma membrane functions in Chinese hamster ovary cells photosensitized by aluminum phthalocyanine.

Ben-Hur E, Dubbelman TM, Van Steveninck J.

Sylvius Laboratory, Department of Medical Biochemistry, Leiden, The Netherlands.

Fluoride inhibits photohemolysis induced by chloroaluminum phthalocyanine tetrasulfonate (AlPcS4) when it is added to dye-loaded human erythrocytes prior to light exposure (E. Ben-Hur, A. Freud, A. Canfi, and A. Livne, Int. J. Radiat. Biol. 59, 797-806, 1991). This is due to formation of a complex of F- with Al3+, leading to selective release and/or modified dye binding with some proteins so that the effective photochemical reaction is prevented. In this work we used F- as a probe to evaluate the involvement of the plasma membrane functions of Chinese hamster ovary cells in photocytotoxicity induced by chloroaluminum phthalocyanine (AlPc). Fluoride was found to protect against killing of cells photosensitized by AlPc but not AlPcS4. Plasma membrane damage induced by AlPc photosensitization was manifested by K+ leakage, membrane depolarization, inhibition of glucose and amino acid uptake, and Na+/K(+)-ATPase inactivation. The latter enzyme system was found to be the one most sensitive to inhibition by the combination of AlPc and PDT among the membrane functions studied, and was completely protected by F- in the dose range at which up to 95% of the cells are killed. Of the other membrane functions only glucose transport was slightly protected by F-. It is concluded that damage to the plasma membrane is involved in cell killing induced by AlPc photosensitization and that the plasma membrane enzyme Na+/K(+)-ATPase is a probable candidate as a critical target.

PMID: 1626048 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1484561&dopt=Abstract

Naunyn Schmiedebergs Arch Pharmacol 1992 Dec;346(6):607-13

Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride.

Lindmar R, Loffelholz K.

Department of Pharmacology, University of Mainz, Federal Republic of Germany.

Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF-4; 10 mM NaF plus 10 microM AlCl3). Atria of rats and chickens were incubated with [3H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [3H]-phosphatidylethanol (PETH) was rapidly formed at the expense of [3H]-PtdOH. This transphosphatidylation reaction is specific for phospholipase D activity. The basal formation of PETH was not inhibited by a Ca(2+)-free, EGTA-containing medium. The phorbol ester 4 beta-phorbol-12 beta, 13 alpha-dibutyrate (PDB), which is known to activate protein kinase C, enhanced the net formation of choline, whereas the inactive 4 beta-phorbol-13 alpha-acetate (PAc) was ineffective. PDB (0.2 microM), in contrast to PAc, also increased the formation of [3H]-PtdOH and, in the presence of ethanol, of [3H]-PETH. The PDB-evoked formation of PETH occurred again at the expense of PtdOH. Treshold and maximum effective concentrations of PDB were 10 nM and 0.2-0.6 microM, respectively. The effects of PDB on either choline efflux and generation of PETH showed the same Ca(2+)-dependency, i.e., both effects were blocked by a Ca(2+)-free, EGTA-containing medium, but not by a Ca(2+)-free medium without EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID: 1484561 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1473246&dopt=Abstract

Carcinogenesis 1992 Dec;13(12):2367-73

Analysis of phospholipid metabolism in murine keratinocytes transformed by the v-ras oncogene: relationship of phosphatidylinositol turnover and cytokine stimulation to the transformed phenotype.

Lee E, Punnonen K, Cheng C, Glick A, Dlugosz A, Yuspa SH.

Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, NIH, Bethesda, MD 20892.

Introduction of a v-rasHa oncogene into cultured mouse keratinocytes by transduction with a defective retrovirus is sufficient to transform keratinocytes to the benign phenotype. Transduced keratinocytes overexpress TGF alpha and hyperproliferate in culture medium with 0.05 mM Ca2+. Whereas normal keratinocytes respond to elevated medium Ca2+ by cessation of proliferation and induction of terminal differentiation, v-rasHa keratinocytes are not induced to differentiate by Ca2+. We now demonstrate that v-rasHa keratinocytes have elevated basal levels of phosphatidylinositol, inositol phosphates and diacylglycerols in 0.05 mM Ca2+ medium. Basal turnover of phosphatidylcholine is not altered by the rasHa oncogene. The generation of inositol phosphates is even further stimulated in v-rasHa cells by an increase in extracellular Ca2+ or by exposure to aluminum fluoride. Thus, the v-rasHa gene product does not stimulate the inositol phospholipid pathway maximally and additional phosphatidylinositol is available for turnover in response to inducers of phospholipase C activity. TGF alpha and medium conditioned by v-rasHa keratinocytes, both of which stimulate proliferation of normal cells in 0.05 mM Ca2+, transiently increased phosphatidylinositol turnover in normal keratinocytes but did not inhibit Ca(2+)-induced terminal differentiation. In contrast, sustained elevation in basal phosphatidylinositol metabolism was produced by aluminum fluoride. Combined exposure to aluminum fluoride and exogenous TGF alpha caused hyperproliferation, resistance to Ca(2+)-induced differentiation and morphological changes identical to those of v-rasHa keratinocytes. These results provide a link between the biological consequences of v-rasHa gene expression and biochemical changes which are known to alter the keratinocyte phenotype.

PMID: 1473246 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1491429&dopt=Abstract

J Membr Biol 1992 Dec;130(3):265-76

G-protein activators induce a potassium conductance in murine macrophages.

McKinney LC, Gallin EK.

Department of Physiology, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145.

The whole-cell patch clamp technique was used to test whether intracellular application of G-protein activators affect ionic currents in murine macrophages. Both the J774.1 macrophage-like cell line and primary bone marrow derived macrophages were used. Cells were bathed in Na Hanks' solution and intracellularly dialyzed (via the patch pipette) with K Hanks (145 mM KCl, < 100 nM Ca) plus or minus the G-protein activators GTP gamma S (10 microM), GppNHp (10 microM), or AIF4- (200 microM AlCl3 + 5 mM KF). In the absence of G-protein activators, only two K currents, an inwardly rectifying K current (Kir) and an outward, inactivating K current (Ko) were observed. In the presence of protein activators, two effects were observed:
(i) the Kir conductance, which is stable for up to 30 min under control conditions, decayed twice as fast and
(ii) an outwardly rectifying, noninactivating current appeared. The induced outward current appeared < 2 min after attaining the whole-cell patch clamp configuration. The current could be distinguished from the Kir and Ko currents on the basis of its direction of rectification (outward), barium sensitivity (> 1 mM), and kinetics (no time-dependent inactivation). Intracellular application of GTP (500 microM), GDP (500 microM), cAMP (100 microM + 0.5 mM ATP), or IP3 (20 microM) did not induce the current; 100 microM ATP gamma S activated a half-maximal amount of current. Induction of outward current by 10 microM GTP gamma S could be prevented by pre-exposing cells to pertussis toxin but not cholera toxin. This current is K selective since
(i) its induction was accompanied by hyperpolarization of the cell toward EK, even after Kir had "washed out",
(ii) it was present after > 90% of both intracellular and extracellular Cl were replaced by isethionate, and
(iii) the induced outward conductance was absent when Ki was completely replaced by Cs, and was reduced by approximately 1/3 when [K]i was reduced by 1/3. Quinidine (1 mM) and 4-aminopyridine (10 mM) inhibited the current, but apamin (1 microM) and charybdotoxin (1 microM) did not.

PMID: 1491429 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1492198&dopt=Abstract

Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove Suppl 1992;35(3):219-42

[Genotoxic activity test of sodium fluoride in vitro]

[Article in Czech]

Srb V, Mrackova G, Kubzova E, Vanickova H, Michalcova I.

Oddeleni geneticke toxikologie Krajske hygienicke stanice v Hradci Kralove.

The artificial drinking water fluoridization provided as a mass preventive measure against dental decay poses another substantial problem which is a possibility of genotoxic action. Up to this date, this matter remains still obscur and is discussed with more or less intensity from time to time. The mentioned fact supported authors to study the impact of short-term 24 hrs sodium fluoride (NaF) action in concentration range of 0-500 mg.1(-1) drinking water in the frame of so-called minimal testing set (analysis of chromosomal aberrations in human peripheral lymphocytes, Ames test). For the initial NaF concentration applied, the reference value of 1 mg per 1 liter artificial fluoridization was estimated. The use of Ames test with TA 98 and TA 100 Salmonella typhimurium (+/- S9) strains showed no significant increase in revertants responsible of NaF mutagenic activity in any of applied concentrations (0-1300 mg per 1 Petri dish; = 0-520 mg.l-1 converted to the basic supplementative dose). Cytogenetic analysis of peripheral lymphocytes showed more sensitivity than prototrofic salmonella test. Yet one order higher NaF concentration than its application norm 1 mg.l-1 (i.e. 11 mg.l-1) has induced the occurrence of 3.8% ABB after single addition for 24 hrs to the "healthy" blood cultivated in vitro at short-term. This accounts for a value close to the level of statistically significant difference with regard to the application norm recommended. This level has been even exceeded as for a total count of fragments and exchanged parts. Thus the two orders higher NaF concentration (110.0 mg.l-1) resulted in a strong increase of cells with chromosomal aberrations for all of indicators observed; e.g. 27.5% ABB. Based on literary sources, obtained results and properly experience in practical proceeding artificial fluoridation, the authors concluded that the latter is not adequate to the up-to-date status of knowledge. Besides of economical and technical problems, those scientific are mainly concerned with making doubtful the auto-presumed genotoxic inertness for chronic users of fluoridated drinking water. Author's opinion is that when necessarily provided, the artificial fluoridization of drinking water should be proceeded selectively (in accord with real requirements of an appropriated population group, its age structure and location), temporarily and with intermittent checkout of fluoridization application regimen. To conclude, authors recommend further observation with use of biological model situations in vivo.

PMID: 1492198 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1312806&dopt=Abstract

Arch Biochem Biophys 1992 Apr;294(1):238-43

A two-step mechanism of fluoride inhibition of rat liver inorganic pyrophosphatase.

Baykov AA, Alexandrov AP, Smirnova IN.

A. N. Belozersky Laboratory of Molecular Biology and Bioorganic Chemistry, Moscow State University, USSR.

Product formation curves for inorganic pyrophosphatase-catalyzed hydrolysis of pyrophosphate in the presence of fluoride were analyzed in order to get insight into the mechanism of its inhibitory action on this enzyme. The enzymatic reaction was monitored with a phosphate analyzer operating on the time scale of seconds. Inhibition patterns were virtually identical for cytosolic and mitochondrial pyrophosphatases. The effect of fluoride was biphasic: it caused a rapid (t 1/2 less than 1 s) decrease in the initial velocity of the reaction followed by slow (t 1/2 greater than or equal to 4 s) inactivation of the enzyme during catalysis. The slow phase resulted in trapping intact substrate at the active site, and the resulting complex could be isolated by gel filtration. Pyrophosphatase remained active when incubated with fluoride in the absence of pyrophosphate or in the presence of its bisphosphonate analogs, which are bound to but not hydrolyzed by this enzyme. These features of the inhibition are consistent with the mechanism in which rapid binding of the inhibitor to the enzyme.substrate complex is followed by its slow isomerization. Kinetic parameters obtained in this work indicate that appreciable inactivation of pyrophosphatase can occur at fluoride concentrations found in human plasma. This effect may therefore be one of the major factors contributing to fluoride toxicity.

PMID: 1312806 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1533644&dopt=Abstract

J Cell Biochem 1992 Apr;48(4):356-66

The inhibition of ATP-dependent shape change of human erythrocyte ghosts correlates with an inhibition of Mg(2+)-ATPase activity by fluoride and aluminofluoride complexes.

Morris MB, Monteith G, Roufogalis BD.

Department of Pharmacy, University of Sydney, Australia.

The vanadate-sensitive Mg(2+)-dependent ATPase activity of the human erythrocyte ghost is believed to be involved in the shape change events that convert echinocytic ghosts to smoothed forms (biconcave discs and stomatocytes). At physiological salt concentration, pH 7.4, 2 mM ATP, 5 mM Mg2+ and 1 mM EGTA, the Mg(2+)-ATPase activity of ghosts was inhibited strongly by millimolar concentrations of sodium fluoride: I50 = 1.31 +/- 0.23 mM (mean +/- S.D.; n = 12). The addition of aluminium chloride to 15 microM reduced the concentration of NaF required for 50% inhibition to 0.76 +/- 0.21 mM (n = 10). Aluminium alone had only a small inhibitory effect on the ATPase activity (13 +/- 9%; n = 10). Desferrioxamine, a strong chelator of tervalent aluminium ion, failed to reverse the inhibition by fluoride and reversed the inhibition in the presence of aluminium and fluoride back to those values obtained with fluoride alone. Of several metal salts tested only beryllium sulfate was able to replace aluminium as an effective inhibitor in the presence of fluoride. Inhibition of the Mg(2+)-ATPase activity by fluoride and the aluminofluoride complexes correlated with an inhibition of the rate of MgATP-dependent change in red cell ghost shape from echinocytes to smoothed forms. All gross morphological changes of the smoothing process were affected, including the production of discocytes, stomatocytes and endocyctic vesicles.

PMID: 1533644 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1315244&dopt=Abstract

Endocrinology 1992 May;130(5):2465-75

Sodium fluoride provokes gonadotrope desensitization to gonadotropin-releasing hormone (GnRH) and gonadotrope sensitization to A23187: evidence for multiple G proteins in GnRH action.

Hawes BE, Marzen JE, Waters SB, Conn PM.

Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242-1109.

Pretreatment of pituitary cell cultures with GnRH causes altered gonadotrope responsiveness to LH secretagogues. The precise mechanism by which this occurs is not understood. Because a G protein appears to be activated after GnRH stimulation of the gonadotrope, a role for this moiety in GnRH-stimulated alterations in gonadotrope responsiveness was assessed. We show that 3 h pretreatment of pituitary cell cultures with 10 mM NaF (a G protein activator), resulted in decreased gonadotrope responsiveness to subsequent GnRH treatment (3 h, 100 nM; 34.4 +/- 1.6% vs. 23.4 +/- 1.5% of total cellular LH). NaF-provoked gonadotrope desensitization to GnRH also occurred in the presence of 3 mM EGTA and in cells which had been depleted of protein kinase C. Desensitization to GnRH did not occur in response to pretreatment with (Bu)2cAMP (8 h, 1 mM). In addition, neither GnRH nor NaF stimulated inositol phosphate production above basal levels after the NaF pretreatment. GnRH receptor binding also decreased by 30% with NaF pretreatment. In contrast, 3 h NaF (10 mM) pretreatment enhanced responsiveness of the gonadotrope to the Ca2+ ionophore A23187 in a protein kinase C- and cAMP-dependent manner. Responsiveness to the phorbol ester, phorbol 12-myristate 13-acetate, was also increased, whereas responsiveness to the Ca2+ channel activator maitotoxin was unchanged. These data suggest that G protein activation by NaF provokes gonadotrope desensitization to GnRH stimulation by both decreasing receptor numbers and by uncoupling of the receptors from inositol phosphate production. In addition, a distinct G protein action appears to be involved in sensitizing the gonadotrope to A23187 and phorbol 12-myristate 13-acetate.

PMID: 1315244 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1644787&dopt=Abstract

J Biol Buccale 1992 Jun;20(2):97-102

Metabolism of glycogen in submandibular glands of rats. Alteration by NaF.

Nicolau J, Ribeiro DM.

Universidade de Sao Paulo, Departamento de Bioquimica, Instituto de Quimica USP, Sao Paulo, Brasil.

Submandibular glands of rats injected with NaF solution (10 mg F-/kg body weight) were analysed for glycogen content and phosphorylase activity after various time intervals. In contrast to what has been reported for the liver, sodium fluoride caused increased glycogen content. Phosphorylase (a and total) activity was not affected, suggesting a different mechanism of action of F- in the submandibular gland. In vivo experiments demonstrated stimulation of glycogenesis.

PMID: 1644787 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1325732&dopt=Abstract

Acta Physiol Scand 1992 Jul;145(3):275-85

Fluoride interactions with stimulus-secretion coupling of normal and pathological parathyroid cells.

Ridefelt P, Hellman P, Rastad J, Larsson R, Akerstrom G, Gylfe E.

Department of Surgery, University of Uppsala, Sweden.

Effects of the GTP binding protein (G-protein) activator NaF on parathyroid hormone (PTH) release, cytoplasmic Ca2+ concentration ([Ca2+]i) and cAMP content of bovine as well as normal and pathological human parathyroid cells were studied using precautions to avoid CaF2 precipitation. In 0.5 mM external Ca2+, NaF inhibited PTH release and lowered the cAMP content by 50-70% of the effects attained with 3.0 mM Ca2+. The NaF-induced increase of [Ca2+]i was considerably smaller than that obtained with rise of external Ca2+. It seems likely that NaF activates the inhibitory G1-protein involved in the regulation of cAMP generation. However, it is unclear whether the sluggish rise of [Ca2+]i induced by NaF is due to a direct effect of a G-protein on Ca2+ entry, or somehow related to the G-protein mediated formation of inositol 1,4,5-trisphosphate, which is part of the signal transduction pathway normally initiated by Ca2+ binding to its receptor on the parathyroid cell surface. Inhibition of PTH release by NaF probably results from the combined effects on [Ca2+]i and cAMP content. In hyperparathyroidism (HPT) the actions of NaF were not markedly affected despite severe impairments of Ca(2+)-inhibited PTH release and Ca2+ triggered increase of [Ca2+]i. Consistent with observations of down regulation of the parathyroid Ca2+ receptor in HPT, the present results indicate that the disease perturbs signal transduction at a level proximal to the site of action for NaF.

PMID: 1325732 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1392294&dopt=Abstract

Bull Environ Contam Toxicol 1992 Jul;49(1):44-50

No Abstract available

Elevated cholinesterase activity and increased urinary excretion of inorganic fluorides in the workers producing fluorine-containing plastic (polytetrafluoroethylene).

Xu B, Zhang J, Mao G, Yang G, Chen A, Aoyama K, Matsushita T, Ueda A.

Department of Industrial Health and Occupational Disease, Faculty of Preventive Medicine, China Medical University, Shenyang.

PMID: 1392294 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1639200&dopt=Abstract

FEBS Lett 1992 Jul 27;307(1):93-6

Brefeldin A and the endocytic pathway. Possible implications for membrane traffic and sorting.

Hunziker W, Whitney JA, Mellman I.

Department of Cell Biology, Yale University School of Medicine, New Haven, CT.

A number of recent observations have suggested that the endocytic and biosynthetic pathways may share fundamentally similar transport mechanisms at the molecular level. Some of the more striking of these suggestions have come from a comparison of the effects of the macrocyclic lactone brefeldin A (BFA) on endosomes and the Golgi complex. BFA is thought to affect Golgi-specific coat proteins that may be involved in maintaining the structural integrity of the organelle and in regulating membrane transport in the secretory pathway. Many of the effects of BFA on the endocytic system, such as the guanine nucleotide and aluminum fluoride (AlF4-)-regulated induction of microtubule-dependent endosomal tubules, are strikingly reminiscent of the action of the drug on the Golgi complex. Therefore, the similar mechanisms of action of the drug on endosomes suggest that organelles of the endocytic pathway may be associated with similar cytoplasmic coats that could regulate endosome function and integrity.

Publication Types:

PMID: 1639200 [PubMed - indexed for MEDLINE]


Full free report available at http://www.pnas.org/cgi/reprint/89/14/6408.pdf

Proc Natl Acad Sci U S A 1992 Jul 15;89(14):6408-12

ADP-ribosylation factor, a small GTP-binding protein, is required for binding of the coatomer protein beta-COP to Golgi membranes.

Donaldson JG, Cassel D, Kahn RA, Klausner RD.

Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

The coatomer is a cytosolic protein complex that reversibly associates with Golgi membranes and is implicated in modulating Golgi membrane transport. The association of beta-COP, a component of coatomer, with Golgi membranes is enhanced by guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), a nonhydrolyzable analogue of GTP, and by a mixture of aluminum and fluoride ions (Al/F). Here we show that the ADP-ribosylation factor (ARF) is required for the binding of beta-COP. Thus, beta-COP contained in a coatomer fraction that has been resolved from ARF does not bind to Golgi membranes, whereas binding can be reconstituted by the addition of recombinant ARF. Furthermore, an N-terminal peptide of ARF, which blocks ARF binding to Golgi membranes, inhibits GTP[gamma S]- as well as the Al/F-enhanced binding of beta-COP. We show that Golgi coat protein binding involves a sequential reaction where an initial interaction of ARF and GTP[gamma S] with the membrane allows subsequent binding of beta-COP to take place in the absence of free ARF and GTP[gamma S]. The fungal metabolite brefeldin A, which is known to prevent the association of coat proteins with Golgi membrane, is shown to exert this effect by interfering with the initial ARF-membrane interaction step.

PMID: 1631136 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1582451&dopt=Abstract

Eur J Pharmacol 1992 Apr 7;214(1):39-44

Aluminum fluoride induces a reversible Ca2+ sensitization in alpha-toxin-permeabilized vascular smooth muscle.

Kawase T, Van Breemen C.

Department of Pharmacology, University of Miami School of Medicine, FL 33101.

The mechanism of aluminumfloride (AlF)-induced Ca2+ sensitization was explored in alpha-toxin-permeabilized rabbit mesenteric artery. In the presence of 0.18 microM Ca2+ and deferoxamine, a strong chelator of aluminum (Al3+), fluoride (F-; applied in the form of NaF) induced very slow tension development, while in the presence of tracer levels of Al3+ tension developed rapidly possibly due to formation of Al-F complexes (especially AlF4-). As a result, AlF significantly shifted the relationship between tension development and free Ca2+ concentration in the Ca(2+)-EGTA buffer (pCa-tension curve) to the left. The rate of the tension development also depended on the EGTA concentration: increasing the EGTA concentration from 0.5 to 10 mM markedly decreased the maximal rate of contraction ((dT/dt)max), probably due to chelation of Al3+ by EGTA, without effect on the maximal tension (delta Tmax). The AlF-induced Ca2+ sensitization could be reversed by extensive washing with relaxing solution (pCa greater than 8), in contrast to the contractions induced by guanosine 5'-[gamma-thio]triphosphate (GTP gamma s; a non-hydrolyzable GTP analogue) or phorbol 12,13-dibutyrate (PDBu) which were irreversible. However, the action of all the compounds appeared to be mediated through a H-7 (1-[5-isoquinolinesulfonyl]-2-methylpiperazine dihydrochloride)-sensitive pathway, and no additive effects among them were observed. In addition, GDP increased (dT/dt)max due to AlF without changing delta Tmax, whereas guanosine 5'-[beta-thio]diphosphate (GDP beta s; a non-hydolyzable GDP analogue) decreased both parameters. These findings suggest that AlF acts on G-proteins to enhance Ca2+ sensitivity of contractile elements through a H-7-sensitive pathway.

PMID: 1582451 [PubMed - indexed for MEDLINE]


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