UNCOUPLING OF BETA-1-ADRENOCEPTORS FROM CARDIAC ADENYLYL-CYCLASE IN CARDIOMYOPATHIC AND CONTROL HAMSTERS

The beta-adrenoceptor-adenylyl cyclase system was studied in heart ven tricles from Wistar rats, cardiomyopathic (BIO 8262) and nonfailing co ntrol hamsters (CLAC) using the beta1-adrenoceptor antagonist CGP 2071 2A. In radioligand binding studies, the majority of beta-adrenoceptors in ventricles from rats as well as from CLAC hamsters was of the beta 1-subtype (72.2% and 76.6%, respectively). In BIO ventricles a signifi cant (CLAC vs. BIO, P < 0.05) reduction in the beta1-subtype (62.9%) w as found. In Wistar rats the subtype-mediated stimulation of adenylyl Cyclase reflected the beta1:beta2 ratio as determined by binding studi es. In hamster ventricles the effect of isoprenaline was mediated pred ominantly (CLAC) or exclusively (BIO) via the beta2-subtype, indicatin g that cardiac beta1-adrenoceptors were partly (CLAC) or completely (B IO) uncoupled from the adenylyl cyclase.