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. The authors 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 phosphatidylinositol (PI) 27%. The divalent ionophore A23187 (5 μM) 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.