A Quantitative Analysis of Beta-Adrenergic Receptor Interactions: Resolution of High and Low Affinity States of the Receptor by Computer Modeling of Ligand Binding Data
Molecular PharmacologyPublished 1 January 1980
Richard S. Kent, ANDRE DE LEAN, Robert J. Lefkowitz
Citations555
SJR quartileQ1
SJR score1.05
SNIP0.78
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TL;DR
The properties of ligand binding to the beta-adrenergic receptor have been studied using a computer modeling technique to analyze data obtained by indirect binding methods and the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity state formed in the presence of the agonist.
Abstract
The properties of ligand binding to the beta-adrenergic receptor have been studied using a computer modeling technique to analyze data obtained by indirect binding methods. Antagonists are shown to bind to the receptor with one homogeneous state of uniform affinity, while agonists manifest heterogeneous binding. For agonists, two distinct binding states are apparent; one of high and one of low affinity. Affinity states of the receptor are characterized by specific macroscopic dissociation constants, and the proportion of total receptors in each state can be determined. The ability of an agonist to activate adenylate cyclase (intrinsic activity) correlates closely with the amount of high affinity state formed in the presence of the agonist (p
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