Diversity of signalling by G protein-coupled receptors

Recent discoveries about signalling via G protein-coupled receptors have re vealed the complexity of this process. Two key factors contribute principal ly to this complexity: the possibility that one single receptor subtype may govern multiple effector pathways, and the fact that a receptor subtype ma y be expressed as a mutant form, or an isoform, due to alternative splicing and RNA editing of the transcript. Whereas it is well established that dif ferent agonists do not necessarily elicit the same magnitude of response, i t is likely that different ligands may also select between several potentia l signal transduction pathways. The diversity of receptor signalling via a single receptor subtype may be a consequence of specific agonist: receptor: G protein interactions. A better understanding of the activation state(s) of the G protein-coupled receptor appears to be essential in order to devel op new ligands, which may either enhance, attenuate, block or reverse a res ponse mediated by a given receptor: effector pathway. Future efforts should not be limited to the study of a receptor under normal conditions, hut als o to its behaviour under pathophysiological conditions. Particularly, furth er investigation is required to understand the relevance of the recently di scovered receptor isoforms.