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Agonist-induced increase in apparent beta-adrenergic receptor size.

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Agonist-induced increase in apparent beta-adrenergic receptor size.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lefkowitz, R. J. Limbird, L. E.
Abstract	The properties of digitonin-solubilized beta-adrenergic receptors from frog erythrocyte membranes were studied by gel exclusion chromatography on AcA 34 Ultragel. beta-Adrenergic receptor binding activity in these membranes can be identified by both an agonist ligand, [(3)H]hydroxybenzylisoproterenol, and the antagonist ligands, [(3)H]dihydroalprenolol and (125)I-labeled hydroxybenzylpindolol. Occupancy of the beta-adrenergic receptors with the [(3)H]hydroxybenzylisoproterenol agonist prior to their solubilization from the membrane leads to an increase in apparent receptor size. Alterations in the molecular size of the receptor cannot be mimicked by occupancy of the binding site with the antagonist ligands. Exposure of frog erythrocyte membranes to [(3)H]hydroxybenzylisoproterenol agonist in the presence of 10 muM Gpp(NH)(p), a guanyl nucleotide analog that exerts multiple regulatory effects on the catecholamine-sensitive adenylate cyclase [ATP pyrophosphate-lyase (cyclizing); EC 4.6.1.1] system, results in the elution of the [(3)H]hydroxybenzylisoproterenol radioligand in both the region characteristic of the agonist-receptor complex and the region characteristic of the antagonist-receptor complex. The precise molecular interactions responsible for the agonist-induced increase in apparent beta-adrenergic receptor size are still unresolved. However, the low concentrations of agonist that are capable of altering apparent receptor size and the sensitivity of this effect to guanyl nucleotides suggest that these phenomena may be intimately involved in eliciting the physiological effects of beta-adrenergic catecholamines at the molecular level.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	75
Language	English
Publisher	National Academy of Sciences
Publisher Date	1978-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adrenergic Beta-Agonists Pharmacology Adrenergic Beta-Antagonists Receptors, Adrenergic, Beta Receptors, Adrenergic Adenylate Cyclase Metabolism Alprenolol Analogs & Derivatives Animals Anura Chromatography, Gel Erythrocyte Membrane Guanylyl Imidodiphosphate Isoproterenol Pindolol Protein Conformation Drug Effects Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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