CHRONIC SYMPATHECTOMY OF CANINE CARDIAC VENTRICLES AFFECTS G(S)-ADENYLYL CYCLASE COUPLING AND MUSCARINIC RECEPTOR DENSITY

The effect of chronic ventricular sympathectomy on sarcolemmal muscari nic receptor (MR) and beta-adrenoceptor densities and coupling of thes e receptors to adenylyl cyclase was examined. Microsomal membranes wer e isolated from right and left ventricles of control dogs (sham- and n onoperated) and dogs with ventricles sympathectomized 4 weeks earlier. Relative to control membranes, MR density was decreased in left but n ot right ventricular (LV, RV) membranes from sympathectomized hearts. Relative carbachol inhibition of adenylyl cyclase was similar in RV an d LV membranes from both heart groups, however. Although beta-adrenoce ptor densities and ratio of beta(1)- and beta(2)-adrenoceptor subtypes did not change, basal adenylyl cyclase activity was 40% less in sympa thectomized membranes as compared with control membranes. Furthermore, relative stimulation of adenylyl cyclase by isoproterenol was twofold greater in sympathectomized heart membranes. Because maximally stimul ated adenylyl cyclase activity by NaF or MnCl2 was identical in sympat hectomized and control membranes, the reduction in basal activity may not be related to a decrease in G(s) and adenylyl cyclase. In support of this hypothesis, G(s alpha) content as estimated from optimal chole ra toxin-catalyzed ADP-ribosylation was similar in control and sympath ectomized membranes. Therefore, an alteration in G(s) interaction with adenylyl cyclase may account for the reduction in basal adenylyl cycl ase activity and the increased relative responsiveness of adenylyl cyc lase to isoproterenol in chronically sympathectomized ventricular memb ranes.