A MODEL OF NONEXCLUSIVE BINDING OF AGONIST AND ANTAGONIST ON G-PROTEIN COUPLED RECEPTORS

A modified concept of functioning of G-protein coupled receptors is presented, on the assumption that agonistic and antagonistic effects of drugs are related to their interaction with two separate receptor sites that exist simultaneously on a single receptor molecule and possess different ligand-specificity patterns. This proposal distinguishes between agonists and antagonists as binding at one of these sites triggers the receptor response, whereas the other site elicits another response leading to the receptor blockade. As these sites are simultaneously present on a single receptor molecule the formation of a ternary complex between agonist, antagonist and receptor is possible. Practical consequences of this concept are analysed with reference to experimental data on muscarinic acetylcholine receptors. (C) 1995 Academic Press Limited