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Cocaine- and amphetamine-regulated transcript encodes an eponymous peptide, CARTp, which exerts diverse pharmacologic actions in the central and peripheral nervous systems, as well as in several endocrine organs, including pancreas. Here we review those diverse actions, the physiological relevance of which had remained unestablished until recently. With the identification of a CARTp receptor, GPR160, the physiologic importance and therapeutic potential of CARTp or analogs are being revealed. Not only is the CARTp-GPR160 interaction essential for the circadian regulation of appetite and thirst but also for the transmission of nerve injury-induced pain. Molecular approaches now are uncovering additional physiologically relevant actions and the development of acute tissue-specific gene compromise approaches may reveal even more physiologically relevant actions of this pluripotent ligand/receptor pair.

Overcoming Stress, Hunger, and Pain: Cocaine- and Amphetamine-Regulated Transcript Peptide’s Promise