Effects of angiotensin II on phosphatidylinositol and polyphosphoinositide turnover in rat kidney. Mechanism of prostaglandin release.
Prostaglandin (PG) release from rat inner medullary tissue has been shown to be stimulated by angiotensin II, bradykinin, and arginine vasopressin. PG release from inner medullary has also been demonstrated to be a Ca2+-dependent process. We performed the following studies in an attempt to determine the mechanism by which angiotensin II stimulates PG release and to identify the lipid source serving as the donor for arachidonic acid (AA) in the Ca2+-dependent reaction. After 5 min of incubation, slices of inner medulla prelabeled with [14C]AA released 2.0-fold as much radiolabel into the media in the presence of Ca2+ as in the absence of Ca2+. After 30 min of incubation, the neutral lipids lost 6.1% of their [14C]AA label, phosphatidylethanolamine lost 12.5%, phosphatidylcholine 13.3%, and phosphatidylinotisol (P[I) 27%. The divalent ionophore A23187 (5 microM) increased 3.7-fold the formation of immunoassayable prostaglandin E2 at 30 min in the presence of Ca2+. Angiotensin II increased immunoassayable PGE2 formation 1.3-fold at 2 min and 1.5- to 1.8-fold by 30 min. In addition, angiotensin II rapidly increased the incorporation of [32P]orthophosphate to significantly higher values into PI, phosphatidic acid, diphosphoinositol, and triphosphoinositol by 30 s, returning to control values by 2 min of incubation. The data suggest that PI may be a major source of arachidonic acid in the Ca2+-dependent release of PG, that angiotensin II stimulates a smaller or different pool of AA release than the divalent ionophore, and the angiotensin II stimulation of PG is a Ca2+-mediated process associated with increased "phosphatidylinositol-polyphosphoinositide" turnover in the rat inner medulla.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D015232:Dinoprostone; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010716:Phosphatidylinositols; D011458:Prostaglandins E; D000804:Angiotensin II; D015232:Dinoprostone; D002118:Calcium