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 pr esented, on the assumption that agonistic and antagonistic effects of drugs are related to their interaction with two separate receptor site s that exist simultaneously on a single receptor molecule and possess different ligand-specificity patterns. This proposal distinguishes bet ween agonists and antagonists as binding at one of these sites trigger s the receptor response, whereas the other site elicits another respon se leading to the receptor blockade. As these sites are simultaneously present on a single receptor molecule the formation of a ternary comp lex between agonist, antagonist and receptor is possible. Practical co nsequences of this concept are analysed with reference to experimental data on muscarinic acetylcholine receptors. (C) 1995 Academic Press L imited