The molecular nature of the acetylcholine receptor: A stereochemical study

Abstract Investigation using CPK and rigid Dore-Jeffs molecular models have made possible specifications of the molecular constituents of the acetylcholine receptor. Evidence exists that structural components of the receptor include protein and phospholipid and it is possible that prostaglandins and Ca 2+ are also involved. The receptor is postulated to be a complex of polypeptide (with arginine and glutamate components) together with nucleophospholipids (of the form G-complementary to glutamate) or C-(complementary to arginine)-P-P-Lipid), prostaglandin and Ca 2+ . The stereochemical data indicates that on this basis, receptors capable of explaining the extensive structure-activity data on cholinergic agonists and antagonists, can be specified for the muscarinic, neuromuscular junction and ganglionic receptors based on different amino acid sequences in the polypeptide. Examples are given of the use of this model to explain structure-activity relationship data. Some predictions made by the hypothesis are presented.