The effects of barbiturates on the metabolism of phosphatidic acid and phosphatidylinositol in rat brain synaptosomes.
Barbiturates and diphenylhydantoin inhibit the carbamoylcholine-stimulated increase in 32P incorporation into phosphatidylinositol and phosphatidic acid, but have a relatively slight effect on the incorporation of 32P into these lipids in the absence of carbamoylcholine and no effect on 32P incorporation into phosphatidylcholine and phosphatidylethanolamine. Inhibition of the carbamoylcholine-stimulated increase was observed for pentobarbital, thiopental, phenobarbital, 5-(1,3-dimethylbutyl)-5-ethylbarbiturate, (+)- and (-)-5-ethyl-N-methyl-5-propylbarbituate and diphenylhydantoin. Similar concentrations of barbiturates and diphenylhydantoin were previously reported to inhibit the K+-stimulated Ca2+ influx, and therefore other agents that affect Ca2+ influx were tested to find whether they had any effect on 32P incorporation into these lipids. K+ (35 mM) increases 32P incorporation into phosphatidic acid, but to a smaller degree than 100 micrometer-carbamoylcholine, and its effect was inhibited by pentobarbital. Veratridine (75 micrometer) does not increase 32P incorporation into either phosphatidic acid or phosphatidylinositol, but did inhibit the carbamoylcholine-stimulated increase in 32P incorporation into phosphatidylinositol. The possible relationship between the phospholipid effect and stimulated Ca2+ influx is discussed.
D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D001463:Barbiturates; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010758:Phosphorus; D010672:Phenytoin; D002217:Carbachol; D010424:Pentobarbital; D002118:Calcium