Receptor subtypes or species homologues: relevance to drug discovery

Cell surface receptors are targets for the pharmacological manipulation of physiological processes and thus represent a key direction for the development of selective therapeutic agents. Traditional pharmacological techniques, together with the development of synthetic ligands, have led to the identification of differences in receptor recognition properties and the proposal of multiple receptor subtypes. Molecular biological studies have confirmed the existence of receptor subtypes within a single species by demonstrating differences in receptor primary sequences. However, equivalent receptors between species also show differences in primary structure, albeit to a much lower degree. This review by Judith Hall and colleagues addresses the question of how differences in receptor primary structure between species relate to changes in pharmacology. The relevance of this to the choice of screens in the testing of potential therapeutic drugs is discussed.