The effects of PGE2 on vasopressin- and guanine nucleotide-mediated adenylate cyclase activity in toad bladder membrane.

Abstract

PGE2 inhibited 10 m U/ml vasopressin-induced osmotic water flow of the toad bladder at 2 x 10-8 M. PGE2 suppressed vasopressin-mediated cyclic AMP accumulation in epithelial cells and also vasopressin-mediated adenylate cyclase activity in a crude homogenate of the cells. However, PGE2 had no effect on cyclic AMP dependent and independent protein phosphorylation. These findings indicate that PGE2 inhibits vasopressin-induced water flow mainly through suppression of adenylate cyclase activity, and that the role of PGE2 at that point in the reaction leading to increased water permeability following cyclic AMP production may be slight. Under conditions in which the hormone and substrate are depleted, PGE2 and guanine nucleotides, such as GTP and Gpp(NH)p, additively bring about an increase in adenylate cyclase activity, toad bladder ; adenylate cyclase ; protein phosphorylation ; vasopressin ; guanine nucleotides ; prostaglandins It is widely accepted that prostaglandin E(PGE) inhibits the vasopressininduced osmotic water flow in the toad urinary bladder (Orloff et al. 1965;Omachi et al. 1974;Schlondorff et al. 1981;. Orloff et al. (1965), Ozer and Sharp (1972) found PGE1 to inhibit the vasopressin-and theophyllineinduced water flow in the toad bladder, but could find no PGE1 effects on the cyclic AMP-induced water flow.They concluded that POE inhibits vasopressin-induced water flow by suppressing adenylate cyclase activity. However, Schlondorff et al. (1981) recently observed that exogenous PGE2 suppresses cyclic AMP-induced water flow following pretreatment of toad bladders with prostaglandin synthesis inhibitors. Thus, it appears that there are two