Inhibition of adenylate cyclase by angiotensin II in rat renal cortex

Abstract

Adenylate cyclase of rat renal cortex was inhibited by angiotensin II (AII). Inhibition required Na+ (100-200 mM) and GTP (10(-8)-10(-4) M) and was opposed by the receptor antagonist [1-sarcosine, 8-isoleucine]AII. The EC50 value (+/- SE)for inhibition by AII was 3.7 +/- 1.2 nM, and the maximum inhibition (+/- SE) was 23 +/- 3%. Inhibition was specific for AII, since both AI and AIII, at concentrations up to 1 microM, were ineffective in producing inhibition. The maximum decrease (+/- SE) in adenylate cyclase activity was from 2.45 +/- 0.08 to 1.78 +/- 0.1 pmol.min/mg protein. A similar absolute decrease was observed when adenylate cyclase was stimulated by calcitonin, vasopressin, or isoproterenol. The inhibition of PTH-stimulated activity [16.7 +/- 0.5 (+/- SE) to 12.2 +/- 0.7 pmol.min/mg protein) was significantly greater than the inhibition of basal activity. Therefore, at least some of the inhibitory angiotensin receptors are coupled to adenylate cyclase molecules which also coupled to receptors for PTH.