Dual effect of fluoride on phosphoinositide metabolism in rat brain cortex. Stimulation of phospholipase C and inhibition of polyphosphoinositide synthesis.
We have studied the effects of fluoride, guanosine 5'-[gamma-thio]triphosphate (GTP[S]) and carbachol on phospholipase C and polyphosphoinositide synthesis. The experimental system consisted of membranes from rat brain cortex, with exogenous [3H]phosphatidylinositol ([3H]PtdIns) as substrate. In such systems, we have not found evidence to support carbachol and/or GTP[S] stimulation of PtdIns phosphorylation. Fluoride inhibited synthesis of PtdIns4P and PtdIns(4,5)P2 from PtdIns. Consequently, under conditions where breakdown of polyphosphoinositides by phospholipase C was dependent on PtdIns kinase activity, fluoride inhibited activation by GTP[S] plus carbachol of phospholipase C. When conditions allowed direct breakdown of PtdIns and precluded PtdIns kinase activity, the stimulatory effects of fluoride and GTP[S] plus carbachol on phospholipase C activity were additive.
Claro
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Department of Biochemistry, University of Tennessee, Memphis 38163.
Wallace
M A
MA
Fain
J N
JN
D019870:1-Phosphatidylinositol 4-Kinase; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000096:biosynthesis* / Q000378:metabolism*; D010770:Phosphotransferases / Q000037:antagonists & inhibitors; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism*
D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D002217:Carbachol; D012969:Sodium Fluoride; D010770:Phosphotransferases; D019870:1-Phosphatidylinositol 4-Kinase; D010738:Type C Phospholipases; D002118:Calcium