CLONING, EXPRESSION, AND TISSUE DISTRIBUTION OF A 5TH MELANOCORTIN RECEPTOR SUBTYPE

The melanocortin (MC) peptides mediate a diverse spectrum of biologica l activities in both the central nervous system and peripheral tissues by interacting with specific guanine nucleotide binding (G protein)-c oupled receptors. Previously, four human melanocortin receptor subtype s have been cloned and characterized. In this study, we have isolated mouse complementary DNA (cDNA) and human genomic clones encoding a fif th melanocortin receptor subtype, MC5. Melanocortin peptide stimulatio n of human MC5, transiently expressed in COS1 cells, results in activa tion of adenylate cyclase with the following sank order of potency: [N le(4), D-Phe(7)]-alpha-MSH (melanocyte stimulating hormone) > ACTH (1- 24) (adrenocorticotropic hormone) > alpha-MSH > beta-MSR > gamma-MSH. Northern blot hybridization, ribonuclease protection, and reverse tran scription/polymerase chain reaction assays indicate that mouse MC5 mRN A is most abundant in skeletal muscle and brain. Lower but detectable levels of MC5 mRNA are also found in RT2-2 retinal neuronal cells, lun g, testis, spleen, heart, kidney, and liver.