IDENTIFICATION OF A RECEPTOR FOR GAMMA-MELANOTROPIN AND OTHER PROOPIOMELANOCORTIN PEPTIDES IN THE HYPOTHALAMUS AND LIMBIC SYSTEM

Corticotropin (ACTH) and melanotropin (MSH) peptides (melanocortins) a re produced not only in the pituitary but also in the brain, with high est concentrations in the arcuate nucleus of the hypothalamus and the commisural nucleus of the solitary tract. We have identified a recepto r for MSH and ACTH peptides that is specifically expressed in regions of the hypothalamus and limbic system. This melanocortin receptor (MC3 -R) is found in neurons of the arcuate nucleus known to express proopi omelanocortin (POMC) and in a subset of the nuclei to which these neur ons send projections. The MC3-R is 43% identical to the MSH receptor p resent in melanocytes and is strongly coupled to adenylyl cyclase. Unl ike the MSH or ACTH receptors, MC3-R is potently activated by gamma-MS H peptides, POMC products that were named for their amino acid homolog y with alpha- and beta-MSH, but lack melanotropic activity. The primar y biological role of the gamma-MSH peptides is not yet understood. The location and properties of this receptor provide a pharmacological ba sis for the action of POMC peptides produced in the brain and possibly a specific physiological role for gamma-MSH.