Neuropeptides are chemical messengers that act to regulate a number of physiological processes, including feeding, reward, pain, and memory, among others. PEN is one of the most abundant hypothalamic neuropeptides; however, until recently, its target receptor remained unknown. In this Review, we summarize recent developments in research focusing on PEN and its receptor GPR83. We describe the studies leading to the deorphanization of GPR83 as the receptor for PEN. We also describe the signaling mediated by the PEN-GPR83 system, as well as the physiological roles in which PEN-GPR83 has been implicated. As studies have suggested a role for the PEN-GPR83 system in food intake and body weight regulation, as well as in drug addiction and reward disorders, a thorough understanding of this novel neuropeptide-receptor system will help identify novel therapeutic targets to treat pathophysiological conditions involving PEN-GPR83.
Keywords: G protein-coupled receptor; de-orphanization; drug addiction; feeding behaviors; hypothalamic signaling; neuropeptide processing.