Witte K, Schnecko A, Olbrich H G, Lemmer B
Center of Pharmacology, J.W. Goethe-University, Frankfurt, Germany.
Eur J Pharmacol. 1995 Jun 23;290(1):1-10. doi: 10.1016/0922-4106(95)90010-1.
Densities of beta-adrenoceptor subtypes and their contributions to stimulation of adenylyl cyclase were studied in heart ventricles from cardiomyopathic (BIO 8262) and control Syrian hamsters (CLAC) at 4 different 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-adrenoceptors was significantly higher in myocardium from 200- and 300-day-old BIO compared to that from age-matched CLAC hamsters. Stimulation of adenylyl cyclase by the non-selective beta-adrenoceptor agonist isoprenaline did not differ between strains, but the beta 1-adrenoceptor mediated component was significantly reduced in cardiomyopathic hamsters of all age groups. In 300-day-old animals beta 1-adrenoceptors accounted for 83% (CLAC) and 68% (BIO) of total beta-adrenoceptor binding sites, whereas only 26% (CLAC) and 6% (BIO) of the isoprenaline effect on cAMP formation were mediated via beta 1-adrenoceptors. Thus, the present study shows a lower coupling efficiency of beta 1-adrenoceptors compared to the beta 2-adrenoceptor subtype in ventricles from healthy Syrian hamsters and a progressive, further reduction in beta 1-adrenergic function in cardiomyopathic animals.
