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.