EFFICIENCY OF BETA-ADRENOCEPTOR SUBTYPE COUPLING TO CARDIAC ADENYLYL-CYCLASE IN CARDIOMYOPATHIC AND CONTROL HAMSTERS

Densities of beta-adrenoceptor subtypes and their contributions to sti mulation of adenylyl cyclase were studied in heart ventricles from car diomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 differ ent ages: 30, 100, 200, and 300 days. In BIO ventricles neither total beta-adrenoceptor density nor that of the beta(1)-adrenoceptor subtype differed from the controls, whereas the density of beta(2)-adrenocept ors was significantly higher in myocardium from 200- and 300-day-old B IO compared to that from age-matched CLAC hamsters. Stimulation of ade nylyl cyclase by the non-selective beta-adrenoceptor agonist isoprenal ine did not differ between strains, but the beta(1)-adrenoceptor media ted component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals beta(1)-adrenoceptors accounte d for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding site s, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta(1)-adrenoceptors. Thus, the pres ent study shows a lower coupling efficiency of beta(1)-adrenoceptors c ompared to the beta(2)-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in beta(1)-adren ergic function in cardiomyopathic animals.