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Differential effects of GTP on the coupling of β-adrenergic receptors to adenylate cyclase from frog and turkey erythrocytes application of new methods for the analysis of receptor-effector coupling
Authors:Lee E Limbird  Andre DeLean  Anne R Hickey  Linda Joy Pike  Robert J Lefkowitz
Institution:1. Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, NC 27710 USA;2. Theoretical Endocrinology Unit, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20014 U.S.A.
Abstract:A detailed comparison of the interaction of β-adrenergic receptors with adenylate cyclase stimulation and modification of this interaction by guanine nucleotides has been made in two model systems, the frog and turkey erythrocyte. Objective analysis of the data was facilitated by the development of new graphical methods which involve the use of logit-logit transformations of percent receptor occupancy versus percent enzyme stimulation plots (coupling curves). Receptor-cyclase coupling in turkey erythrocyte membranes demonstrates a proportional relationship between receptor occupancy and adenylate cyclase activation and is unaffected by exogenous guanine nucleotides. By comparison, the proportional relationship of receptor occupancy and adenylate cyclase activation observed in frog erythrocyte membranes in the absence of guanine nucleotides is modified by the addition of exogenous guanine nucleotides such that a greater fractional enzyme stimulation is elicited by low receptor occupancy. Methodological criteria crucial for valid comparison of receptor occupancy and adenylate cyclase activity are delineated. In addition, the possible molecular mechanisms of receptor-cyclase coupling which might give rise to the coupling curves observed are discussed.
Keywords:Receptor-effector coupling  Catecholamine  β-Adrenergic receptor  Adenylate cyclase  Guanyl nucleotide  (Data analysis  Erythrocyte)  Gpp(NH)p  guanyl-5′-yl-imidodiphosphate
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