Fluoride inhibits agonist-induced formation of inositol phosphates in rat cortex.
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.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000032:analysis; D006168:Guinea Pigs; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D013403:Sugar Phosphates / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D012701:Serotonin; D002217:Carbachol; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D005459:Fluorides; D011188:Potassium; D009638:Norepinephrine