Regulation of beta-adrenergic receptors by guanyl-5'-yl imidodiphosphate and other purine nucleotides.

摘要: Guanyl-5'-yl imidodiphosphate (Gpp(NH)p), GTP, and other purine nucleotides selectively decrease the binding affinity of beta-adrenergic receptors frog erythrocyte membranes for agonists but not antagonists. Shifts in were assessed by determining ability unlabeled ligands to compete with (-)-[3H]dihydroalprenolol membrane-bound receptors. The magnitude the"right" shift displacement curve any 13 tested was directly related intrinsic activity (maximal stimulatory capacity) that agent stimulation membrane adenylate cyclase. Thus, Gpp(NH)p-induced shifts greatest full such as isoproterenol, intermediate partial soterenol, no observed antagonists propranolol. only preparations where agonist leads "coupling" In solubilized cyclase are functionally "uncoupled", Gpp(NH)p did cause right receptor curves. particulate Km identical its effect on affinity, 1 2 muM. Moreover, several paralleled their previously determined affinities nucleotide regulatory sites also shifted dose-response curves cyclase, left. As effects curves, "apparent affinities" enzyme activities. markedly increased agonists. These results appear indicate conformational alterations caused occupation capable inducing induced when "coupled" virtue binding. nucleotide-altered conformation is characterized decreased functional efficacy stimulating enzyme.