Uncoupling of beta 1-adrenoceptors from cardiac adenylyl cyclase in cardiomyopathic and control hamsters

Eur J Pharmacol. 1993 Oct 15;247(2):215-8. doi: 10.1016/0922-4106(93)90080-s.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenylyl Cyclases / metabolism*
  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Binding, Competitive / drug effects
  • Cardiomyopathies / enzymology
  • Cardiomyopathies / metabolism*
  • Cricetinae
  • Heart Ventricles / enzymology
  • Heart Ventricles / metabolism
  • Imidazoles / pharmacology
  • Isoproterenol / pharmacology
  • Male
  • Membranes / enzymology
  • Membranes / metabolism
  • Mesocricetus
  • Myocardium / enzymology
  • Myocardium / metabolism
  • Propanolamines / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-1 / metabolism*

Substances

  • Adrenergic beta-Antagonists
  • Imidazoles
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • CGP 20712A
  • Adenylyl Cyclases
  • Isoproterenol
  • CGP 12177
  • 1-Methyl-3-isobutylxanthine