Tumor promoter 12-O-tetradecanoylphorbol 13-acetate inhibits mas/angiotensin receptor-stimulated inositol phosphate production and intracellular Ca2+ elevation in the 401L-C3 neuronal cell line

Abstract

Stimulation of mas-oncogene transfected 401L-C3 cells by angiotensins leads to the production of inositol phosphates. This response shows dose dependence, and has an apparent rank order of potency angiotensin III greater than or equal to angiotensin II much greater than angiotensin I. Preincubation with 12-O-tetradecanoylphorbol 13-acetate, for 5 min, significantly diminishes both inositol phosphate and intracellular [Ca2+] responses to angiotensins, without affecting those stimulated by the endogenous bradykinin receptor. Incubation of 401L-C3 cells with either phorbol ester or angiotensins leads to elevation of intracellular pH, implying that mas/angiotensin receptor stimulation itself leads to protein kinase C activation. These results suggest the operation of a negative feedback loop specific for the mas/angiotensin receptor signalling pathway, and which may be essential in defining the final biological output response to this receptor stimulation.