INTERACTION BETWEEN G-PROTEIN-OPERATED RECEPTORS ELICITING SECRETION IN RAT ADRENALS - A POSSIBLE ROLE OF PROTEIN-KINASE-C

Catecholamine release induced by angiotensin II, histamine, bradykinin and methacholine from the rat adrenal gland perfused in vitro was stu died under conditions in which the activity of protein kinase C (PKC) was modified. Perfusion of glands with 10 nM bradykinin abolished, in a reversible way, the secretion induced by short pulses of angiotensin II, histamine and methacholine bur. did not modify the release evoked by 23.6 mM KCl (high K+). Perfusion with histamine or methacholine (3 0 mu M) inhibited the secretion induced by the other agents by 30-50%, whereas incubation with angiotensin II (100 nM) caused little or no r eduction in the release evoked by the other agents. The treatment of g lands with 1 nM of the PKC activator phorbol 12,13-dibutyrate (PDBu) s uppressed the responses induced by angiotensin II, histamine and metha choline, did not affect those evoked by bradykinin, and potentiated th e secretion evoked by high K+. The adenylate cyclase stimulator forsko lin (1 mu M) did not affect the basal secretion but strongly potentiat ed the release evoked by all secretagogues used, suggesting a role for protein kinase A (PKA) downstream of the receptor. The PKC inhibitor Ro-31-8220 partially reversed the inhibitory effect of bradykinin. C)u r results suggest that angiotensin II, histamine and muscarinic recept ors share some common transduction mechanism that is regulated by PKC. PKC activity was enhanced by these agents PDBu much greater than brad ykinin = histamine > methacholine = angiotensin II. Bradykinin recepto r transduction does not appear to be regulated by PKC. Copyright (C) 1 997 Elsevier Science Inc.