G-protein coupled receptor 160, GP160 or GPR160, is an orphan class A GPCR that plays a role in pain signaling.^1,3

GPR160 is composed of 338 amino acids, encoded by 7 exons located at 3q26.2-q27, demonstrates a significant degree of conservation across various species, and is expressed in neurons, astrocytes, and microglia within the central nervous system (CNS) and spinal cord.³

Cocaine- and amphetamine-regulated transcript peptide (CARTp) exhibits various pharmacological actions in the CNS, peripheral nervous system, and several endocrine organs. It plays a role in reward and addiction, anxiety and depression, and food intake and body weight maintenance. It has been found that the interaction between CARTp and GPR160 is essential for the circadian regulation of appetite and thirst as well as the transmission of pain signals induced by nerve injury. GPR160 has been shown to confer CARTp-induced cFOS and ERK phosphorylation and activation of CREB independently of cAMP signaling. ERK can function as an upstream regulator of CREB phosphorylation during the development of neuropathic pain. As a putative ligand for GPR160, endogenous CARTp inhibition has been shown to mitigate neuropathic pain.^1,2

GPR160 has also been shown to play a role in the pathogenesis of prostate cancer. Transcription profiles demonstrate a marked increase of GPR160 mRNA in all stages of prostate cancer samples and cancer cell lines, except prostate hyperplasia tissues, with levels comparable to those in stage II-IV cancer patients. GPR160 knockdown increased caspase 1 and IL-6 expression and induced cell cycle arrest and apoptosis. The involvement of GPR160 in prostate carcinogenicity has therapeutic implications for exploring diagnostics and pharmaceutical interventions.³