Uncoupling of beta 1-adrenoceptors from cardiac adenylyl cyclase in cardiomyopathic and control hamsters.
The beta-adrenoceptor-adenylyl cyclase system was studied in heart ventricles from Wistar rats, cardiomyopathic (BIO 8262) and nonfailing control hamsters (CLAC) using the beta 1-adrenoceptor antagonist CGP 20712A. 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 significant (CLAC vs. BIO, P < 0.05) reduction in the beta 1-subtype (62.9%) was found. In Wistar rats the subtype-mediated stimulation of adenylyl cyclase reflected the beta 1:beta 2 ratio as determined by binding studies. In hamster ventricles the effect of isoprenaline was mediated predominantly (CLAC) or exclusively (BIO) via the beta 2-subtype, indicating that cardiac beta 1-adrenoceptors were partly (CLAC) or completely (BIO) uncoupled from the adenylyl cyclase.
Witte
K
K
Center of Pharmacology, J.W. Goethe-University, Frankfurt, Germany.
Olbrich
H G
HG
Langer
L
L
Lemmer
B
B
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D009202:Cardiomyopathies / Q000201:enzymology / Q000378:metabolism*; D006224:Cricetinae; D006352:Heart Ventricles / Q000201:enzymology / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000201:enzymology / Q000378:metabolism; D008647:Mesocricetus; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D007093:Imidazoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; C049763:CGP 20712A; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C033394:CGP 12177; D015056:1-Methyl-3-isobutylxanthine