title: In vivo regulation of beta-adrenergic receptors on mononuclear leukocytes and heart. Assessment of receptor compartmentation after agonist infusion and acute aortic constriction in guinea pigs.
abstract: In animals injected with a bolus of isoproterenol, beta-adrenergic receptors in both mononuclear leukocytes (MNL) and heart were sequestered away from the cell surface, and the time course (0-120 min) and dose-response patterns were similar in the two tissues. In guinea pigs given a constant infusion of isoproterenol, 0.15 mg/(kg.h), down-regulation of total receptor number occurred more quickly and to a greater extent in the MNL than in the heart. We also compared receptor sequestration after aortic constriction-induced acute heart failure. Negligible sequestration (9%) of beta-adrenergic receptors occurred in the MNL of animals treated in this manner, whereas the number of receptors in the sarcolemmal fraction decreased 61%. This selective sequestration of cardiac receptors may result from the action of high concentrations of norepinephrine (which is selective for beta 1 over beta 2 receptors) present at sympathetic nerve-cardiac cell synapses. We conclude that although receptor redistribution occurs similarly in MNL and heart in response to a circulating nonselective agonist, beta-adrenergic receptor redistribution may occur selectively in the heart in response to such stimuli as aortic constriction-induced acute heart failure that activate the sympathetic nervous system.
authors.affiliation: Department of Pharmacology, University of California, San Diego 92093.
authors.forename: A S
authors.initials: AS
authors.lastname: Maisel
authors.forename: M G
authors.initials: MG
authors.lastname: Ziegler
authors.forename: S
authors.initials: S
authors.lastname: Carter
authors.forename: P A
authors.initials: PA
authors.lastname: Insel
authors.forename: H J
authors.initials: HJ
authors.lastname: Motulsky
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002451:Cell Compartmentation; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014661:Vasoconstriction
chemical_list: D011943:Receptors, Adrenergic, beta; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D009638:Norepinephrine