THE EFFECT OF ARGININE VASOPRESSIN AND ITS ANALOGS ON THE SYNTHESIS OF PROSTAGLANDIN-E2 BY RAT RENAL MEDULLARY INTERSTITIAL-CELLS IN CULTURE

Abstract

Arginine vasopressin (AVP) stimulates renal prostaglandin (PG) production which is thought to inhibit vasopressin''s antidiuretic action. Using rat renal medullary cells in culture (RMIC), the ability of the following peptides which possess different biological activities to stimulate PG biosynthesis were compared: AVP (high antidiuretic and pressor activities); 1-desamino-8-D-arginine vasopressin (a synthetic peptide with high antidiuretic and no pressor activity) and oxytocin (intermediate pressor, low antidiuretic activity). Radiometric TLC of supernatant media from cells incubated with octatritiated or [14C]arachidonic acid revealed only 1 radiolabeled peak which co-migrated with PGE2. Radioimmunoassay confirmed that PGE2 was the only PG synthesized by RMIC. Incubation of cells with AVP (1 nM to 3 .mu.M) increased PGE2 synthesis measured by radioimmunoassay in a concentration-dependent fashion up to 2 1/2-fold over control; 1-desamino-8-D-arginine did not increase PGE2 synthesis. Oxytocin stimulated PGE2 synthesis, but was less potent than AVP. Preincubation of RMIC with [1-(.beta.-mercapto-.beta.,.beta.-cyclopentamethylene propionic acid)-4-valine, 8-D-arginine]vasopressin, a synthetic nonpressor, nonantidiuretic antagonist of AVP''s pressor activity, completely blocked the ability of AVP to stimulate PGE2 synthesis. The ability of AVP to stimulate PGE2 synthesis in RMIC is related to its pressor, not its antidiuretic, activity.