Differential regulation of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system after chronic (-)-isoproterenol infusion.
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.
Molenaar
P
P
Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia.
Smolich
J J
JJ
Russell
F D
FD
McMartin
L R
LR
Summers
R J
RJ
D000818:Animals; D001345:Autoradiography; D005260:Female; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000737:chemistry / Q000187:drug effects*; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D011433:Propranolol; D010869:Pindolol; D007545:Isoproterenol