The ORL₁ receptor: Molecular pharmacology and signalling mechanisms

The cloning of the opioid-receptor-like 1 (ORL₁) 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 ORL₁ 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 ORL₁ receptor and its signalling pathways, as well as document the efforts to produce high-affinity selective ligands for the ORL₁ receptor that may be of value as research and therapeutic tools.