The ORL1 receptor: molecular pharmacology and signalling mechanisms

The cloning of the opioid-receptor-like 1 (ORL(1)) receptor and the identification of nociceptin as its endogenous agonist have revealed a new G-protein-coupled receptor signalling system. The structural and functional homology of ORL(1) to the opioid receptor systems has posed a number of challenges in understanding the often competing physiological responses elicited by these G-protein-coupled receptors. Thus, this review will attempt to summarize recent research by many groups that has revealed numerous subtleties of the ORL(1) receptor and its signalling pathways, as well as document the efforts to produce high-affinity selective ligands for the ORL(1) receptor that may be of value as research and therapeutic tools.