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 studied 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 but did not modify the release evoked by 23.6 mM KCl (high K+). Perfusion with histamine or methacholine (30 microM) inhibited the secretion induced by the other agents by 30-50%, whereas incubation with angiotensin II (100 nM) caused little or no reduction in the release evoked by the other agents. The treatment of glands with 1 nM of the PKC activator phorbol 12,13-dibutyrate (PDBu) suppressed the responses induced by angiotensin II, histamine and methacholine, did not affect those evoked by bradykinin, and potentiated the secretion evoked by high K+. The adenylate cyclase stimulator forskolin (1 microM) did not affect the basal secretion but strongly potentiated 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. Our results suggest that angiotensin II, histamine and muscarinic receptors share some common transduction mechanism that is regulated by PKC. PKC activity was enhanced by these agents PDBu >> bradykinin = histamine > methacholine = angiotensin II. Bradykinin receptor transduction does not appear to be regulated by PKC.
Alvarez
C
C
Departamento de Farmacología y Medicina Física, Facultad de Medicina,Universidad de la Laguna, Tenerife, Spain.
Lorenzo
C
C
Santana
F
F
Borges
R
R
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002395:Catecholamines; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins