Chronic sympathectomy of canine cardiac ventricles affects Gs-adenylyl cyclase coupling and muscarinic receptor density

Abstract

The effect of chronic ventricular sympathectomy on sarcolemmal muscarinic receptor (MR) and beta-adrenoceptor densities and coupling of these receptors to adenylyl cyclase was examined. Microsomal membranes were isolated from right and left ventricles of control dogs (sham- and nonoperated) and dogs with ventricles sympathectomized 4 weeks earlier. Relative to control membranes, MR density was decreased in left but not right ventricular (LV, RV) membranes from sympathectomized hearts. Relative carbachol inhibition of adenylyl cyclase was similar in RV and LV membranes from both heart groups, however, Although beta-adrenoceptor densities and ratio of beta 1- and beta 2-adrenoceptor subtypes did not change, basal adenylyl cyclase activity was 40% less in sympathectomized membranes as compared with control membranes. Furthermore, relative stimulation of adenylyl cyclase by isoproterenol was twofold greater in sympathectomized heart membranes. Because maximally stimulated adenylyl cyclase activity by NaF or MnCl2 was identical in sympathectomized and control membranes, the reduction in basal activity may not be related to a decrease in Gs and adenylyl cyclase. In support of this hypothesis, Gs alpha content as estimated from optimal cholera toxin-catalyzed ADP-ribosylation was similar in control and sympathectomized membranes. Therefore, an alteration in Gs interaction with adenylyl cyclase may account for the reduction in basal adenylyl cyclase activity and the increased relative responsiveness of adenylyl cyclase to isoproterenol in chronically sympathectomized ventricular membranes.