Prostaglandin synthesis linked to phosphatidylinositol turnover in isolated rat glomeruli.
Prostaglandins produced by the glomerulus are important factors in controlling glomerular function. The controlling step, i.e., the release of arachidonic acid from the phospholipids by either phospholipase A2 and/or C, remains poorly defined. The present studies were designed to determine which factors control arachidonic acid turnover and prostaglandin synthesis in glomeruli. As tools we used the calcium ionophore A23187, mepacrine, a phospholipase inhibitor, trifluoperazine, a calmodulin antagonist, and angiotensin II. A23187 (2 microM) caused a significant stimulation of both prostaglandin E2 and prostaglandin F2 alpha synthesis (measured by radioimmunoassay), which was associated with increased phosphatidylinositol turnover (measured by [14C]arachidonic acid and [32P]orthophosphate incorporation). Surprisingly, trifluoperazine (10-100 microM) also progressively increased synthesis of both prostaglandins, which was accompanied by increased phosphatidic acid/phosphatidylinositol turnover and decreased phosphatidylinositol content. In contrast, phosphatidylcholine and phosphatidylethanolamine turnover were significantly inhibited by trifluoperazine and their total content remained unaffected. Mepacrine (1 mM) decreased prostaglandin synthesis and both phosphatidylcholine and phosphatidylethanolamine turnover, and had no consistent effect on phosphatidylinositol turnover in control glomeruli. Mepacrine did, however, inhibit both A23187 or trifluoperazine-induced increase in phosphatidylinositol turnover. Angiotensin II increased turnover of phosphatidylinositol and also phosphatidylcholine, as determined by incorporation of [14C]arachidonic acid. Thus, all agents that increased prostaglandin synthesis also enhanced phosphatidylinositol turnover. The exact pathway of arachidonic acid release remains to be determined.
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D010710:Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011453:Prostaglandins / Q000096:biosynthesis*; D011796:Quinacrine / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology
D001095:Arachidonic Acids; D010710:Phosphates; D010716:Phosphatidylinositols; D011453:Prostaglandins; D000804:Angiotensin II; D014268:Trifluoperazine; D016718:Arachidonic Acid; D000001:Calcimycin; D011796:Quinacrine