BIOCHEMICAL STUDIES ON MUSCARINIC ACETYLCHOLINE RECEPTORS

This review presents the results which have emerged from studies of the agonist and antagonist binding properties of muscarinic receptors, and considers the compatibility of these results with the picture of receptor function derived from study of physiological and biochemical responses. The successful detection and characterization of agonist and antagonist binding to muscarinic receptors in vitro, in itself represents a considerable advance. The binding studies have led to a simple and internally consistent picture of the interactions of agonists and antagonists with the receptor. In the case of antagonists, this picture is complementary to that provided by pharmacological studies. In the case of agonists, no comparably simple relationship holds between the in vitro parameters and the parameters derived from pharmacological experiments, even though there are clearcut correlations between the 2 sets of data. This raises the question of whether the in vitro studies of the binding of agonists to tissue homogenates accurately reflect the agonist binding properties of the receptor in whole tissue. The available evidence does not contradict this supposition. The presence of a heterogeneous population of agonist binding sites in whole tissue, as in homogenates, would therefore conflict with the assumption of simple mass action binding, which has formed the basis for pharmacological analysis of whole tissue responses.