Efficiency of beta-adrenoceptor subtype coupling to cardiac adenylyl cyclase in cardiomyopathic and control hamsters.
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.
Witte
K
K
Center of Pharmacology, J.W. Goethe-University, Frankfurt, Germany.
Schnecko
A
A
Olbrich
H G
HG
Lemmer
B
B
D000262:Adenylyl Cyclases / Q000032:analysis*; D000367:Age Factors; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D006224:Cricetinae; D008647:Mesocricetus; D009206:Myocardium / Q000737:chemistry*; D018342:Receptors, Adrenergic, beta-1 / Q000032:analysis*; D018343:Receptors, Adrenergic, beta-2 / Q000032:analysis*
D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D000262:Adenylyl Cyclases