GPCR deorphanizations: the novel, the known and the unexpected transmitters

Pairing orphan G-protein-coupled receptors (GPCRs) to potential ligands found in tissue extracts or in libraries of synthetic compounds has identified an ever-increasing number of transmitters, some of which are novel, some of which were previously known and, more recently, some of which are unexpected. These discoveries raise questions about the nature of transmitters and the specificity of GPCRs. In this article, several aspects of the impact of orphan GPCR research on our understanding of the diversity of transmitters will be discussed.