Open AccessAgonist-induced increase in apparent β-adrenergic receptor size
Author(s) -
Lee E. Limbird,
Robert J. Lefkowitz
Publication year - 1978
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.75.1.228
Subject(s) - agonist , digitonin , receptor , chemistry , radioligand , partial agonist , adenylate kinase , competitive antagonist , alprenolol , radioligand assay , adrenergic receptor , biophysics , medicine , biochemistry , biology , membrane
The properties of digitonin-solubilized β-adrenergic receptors from frog erythrocyte membranes were studied by gel exclusion chromatography on AcA 34 Ultragel. β-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 and125 I-labeled hydroxybenzylpindolol. Occupancy of the β-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 μM 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 β-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 β-adrenergic catecholamines at the molecular level.