Angiotensin II enhances the expression of Giα in A10 cells (smooth muscle):: Relationship with adenylyl cyclase activity

In the present studies, we have investigated the effect of angiotensin II (AII) on guanine nucleotide regulatory protein (G protein) expression and functions in A10 smooth muscle cells. AII treatment of A10 cells enhanced the levels of inhibitory guanine nucleotide regulatory protein (Gi) as well as Gi mRNA and not of stimulatory guanine nucleotide regulatory protein (Gs) in a concentration-dependent manner as determined by immunoblot and Northern blot analysis, respectively. ATI-evoked increased expression of Gi alpha-2 and Gi alpha-3 was inhibited by actinomycin D treatment (RNA synthesis inhibitor). The increased expression of Gi alpha-2 and Gi alpha-3 by AII was not reflected in functions, because the GTP gamma S-mediated inhibition of forskolin-stimulated adenylyl cyclase and the receptor-mediated inhibition of adenylyl cyclase by AII and C-ANP(4-23) [des(Gln(18), Ser(19), Gln(20), Leu(21), Gly(22)) ANP(4-23)-NH2] were not augmented but attenuated in AII-treated A10 cells, The attenuation was prevented by staurosporine (a protein kinase C inhibitor) treatment. On the other hand, AII treatment did not affect the expression and functions of stimulatory guanine nucleotide regulatory protein (Gs), however, the stimulatory effects of 5'-O-(3-thiotriphosphate), isoproterenol, and N-ethylcarboxamide adenosine (NECA) on adenylyl cyclase activity were inhibited to various degrees by AII treatment, Staurosporine reversed the AII-evoked attenuation of isoproterenol- and NECA-stimulated enzyme activity. From these results, it can be suggested that AII, whose levels are increased in hypertension, may be one of the possible contributing factors responsible for exhibiting an enhanced expression of Gi protein in hypertension, (C) 1999 Academic Press.