Angiotensin II receptors negatively coupled to adenylate cyclase in rat myocardial sarcolemma: Involvement of inhibitory guanine nucleotide regulatory protein

Abstract

The effect of angiotensin II (AII) on adenylate cyclase was studied in the rat and rabbit heart sarcolemma. AII inhibited adenylate cyclase activity in the rat and rabbit sarcolemma in a concentration-dependent manner. Maximal inhibition of about 35–40% was observed in the rat, with an apparent K i of about 3 nM; about 30% inhibition, with an apparent K i of about 6 nM, was noted in rabbit sarcolemma. The inhibitory effect of AII was dependent on the presence of guanine nucleotides and was blocked by saralasin. In addition, AII also inhibited the stimulatory effects of isoproterenol and glucagon on adenylate cyclase. Ninhibin, a sperm factor which has been shown to modify the characteristics of inhibitory guanine nucleotide regulatory protein (G i), attenuated the inhibitory effects of AII on basaL and hormone-sensitive adenylate cyclase. Furthermore, pertussis toxin (PT) treatment of the sarcolemma in the presence of [ 32P]NAD resulted in ADP-ribosylation of a single 41-kD protein. PT also attenuated the AII-mediated inhibition of basal and hormone-sensitive adenylate cyclase and enhanced the magnitude of the stimulatory effects of isoproterenol and glucagon on adenylate cyclase activity. These data suggest that the rat myocardial sarcolemma contains AII receptors that are negatively coupled to adenylate cyclase through G i protein.