Angiotensin AT(1) receptors in Clone 9 rat liver cells: Ca2+ signaling andc-fos expression

In C9 (Clone 9) liver cells, angiotensin II increased the intracellular Ca2 + content, inositol phosphate production and c-fos mRNA expression. Other a ngiotensins were also active with the order of potency being angiotensin II = angiotensin III>> angiotensin I > angiotensin IV. Losartan, but not PD 12 3177 (1 -(4-amino-3-methyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imidazo [4,5 c]pyridine-6-carboxylic acid), blocked the effects of angiotensin II. Pertussis toxin did not alter these actions of angiotensin II. These data i ndicate that the effects were mediated through angiotensin AT(1) receptors involving pertussis toxin-insensitive G-proteins. Phorbol myristate acetate was also able to increase c-fos mRNA expression. The action of angiotensin II was consistently greater than that of the active phorbol ester. Stauros porine but not genistein inhibited this effect of angiotensin II. Angiotens in II- and phorbol myristate acetate-induced proto-oncogene mRNA expression was attenuated in cells incubated overnight with the active phorbol ester, which suggests a major role of protein kinase C. (C) 1998 Elsevier Science B.V. All rights reserved.