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

The effect of chronic ventricular sympathectomy on sarcolemmal muscarinic receptor (MR) and β-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 sym-pathectomized 4 weeks earlier. Relative to control membranes, MR density was decreased in left but not right ventricular (LV, RV) membranes from sympathecto-mized hearts. Relative carbachol inhibition of adenylyl cyclase was similar in RV and LV membranes from both heart groups, however. Although β-adrenoceptor densities and ratio of β₁- and β₂-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 sym-pathectomized heart membranes. Because maximally stimulated adenylyl cyclase activity by NaF or MnCl₂was identical in sympathectomized and control membranes, the reduction in basal activity may not be related to a decrease in G_sand adenylyl cyclase. In support of this hypothesis, G_sαcontent as estimated from optimal cholera toxin-catalyzed ADP-ribosylation was similar in control and sympathectomized membranes. Therefore, an alteration in G_sinteraction 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.