Differential regulation of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system after chronic (-)-isoproterenol infusion

J Pharmacol Exp Ther. 1990 Oct;255(1):393-400.

Abstract

Quantitative autoradiography was used to determine the effects of chronic administration of (-)-isoproterenol (400 micrograms/kg/hr, 7 days) on the distribution and density of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system and surrounding regions. X-ray film was exposed to sections of heart labeled with (-)-[125I]-cyanopindolol in the absence or presence of ICI 118,551 (70 nM) to block beta-2 adrenoceptors, CGP 20712A (100 nM) to block beta-1 adrenoceptors or (-)-propranolol (1 microM) to define nonspecific binding. Quantitative autoradiography was performed using computer-assisted image processing and the AVID system. The proportions of beta-1 and beta-2 adrenoceptors were determined by the extent of inhibition of (-)-[125I]cyanopindolol binding by CGP 20712A (100 nM) together with equations which take into account the differing affinities of ligands for beta-1 and beta-2 adrenoceptors. In vehicle (1 mM HCl)-treated animals there was a higher density and proportion of beta-2 adrenoceptors in the atrioventricular node, bundle of His and right and left bundle branches than in myocardium. Chronic administration of (-)-isoproterenol produced marked loss of beta-2 adrenoceptor binding in all regions of the atrioventricular conducting system, surrounding myocardium, cardiac valves and the smooth muscle of the aorta accompanied by less pronounced effects on beta-1 adrenoceptors. Beta-1 adrenoceptors were significantly reduced only in the left bundle branch whereas there were trends toward a reduction in the right bundle branch, bundle of His and an increase in the atrioventricular node. There was no alteration in beta-1 adrenoceptor density in myocardium. Loss of beta adrenoceptor binding produced by (-)-isoproterenol was mainly confined to beta-2 adrenoceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Female
  • Guinea Pigs
  • Heart Conduction System / chemistry
  • Heart Conduction System / drug effects*
  • Iodocyanopindolol
  • Isoproterenol / administration & dosage
  • Isoproterenol / pharmacology*
  • Male
  • Pindolol / analogs & derivatives
  • Pindolol / metabolism
  • Propranolol / pharmacology
  • Receptors, Adrenergic, beta / analysis
  • Receptors, Adrenergic, beta / drug effects*

Substances

  • Receptors, Adrenergic, beta
  • Iodocyanopindolol
  • Propranolol
  • Pindolol
  • Isoproterenol