Chronic beta 1-adrenoceptor antagonist treatment sensitizes beta 2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium

Br J Pharmacol. 1990 Oct;101(2):363-9. doi: 10.1111/j.1476-5381.1990.tb12715.x.


1. In 64 patients undergoing coronary artery bypass grafting the effects of chronic beta 1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial beta-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated. 2. The beta 1-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3. Concomitantly, activation of right atrial adenylate cyclase by 10 microM GTP, 10 microM isoprenaline and 1 microM forskolin was enhanced and inhibition by 100 microM carbachol was diminished. 4. On isolated, electrically driven right atria the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was - even with beta 1-adrenoceptor number increased - not altered, while the beta 2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased. 5. It is concluded that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number and concomitantly sensitizes beta 2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adrenergic beta-Agonists / pharmacology
  • Adrenergic beta-Antagonists / pharmacology*
  • Adult
  • Aged
  • Carbachol / antagonists & inhibitors
  • Female
  • Heart Atria / drug effects*
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects
  • Radioligand Assay
  • Receptors, Adrenergic, beta / drug effects*
  • Receptors, Muscarinic / drug effects*
  • Time Factors


  • Adenylyl Cyclase Inhibitors
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Receptors, Muscarinic
  • Carbachol