Molecular Cloning, Expression, and Characterization of a Fifth Melanocortin Receptor

Abstract

We report the isolation of a gene encoding a novel member of the family of melanocortin receptors. The mouse melanocortin-5 receptor (mMC5R) responds to melanocortins with an increase in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) concentrations. Stimulation of the mMC5R by the melanocortins revealed a hierarchy of potency in which alpha-melanocyte stimulating hormone (alpha-MSH) > beta-melanocyte stimulating hormone (beta-MSH) > adrenocorticotropic hormone (ACTH) > gamma- melanocyte stimulating hormone (gamma-MSH). Further structure-activity studies indicated that amino- and carboxyl-terminal portions of alpha-MSH appear to be key determinants in the activation of mMC5R whereas the melanocortin core heptapeptide sequence is devoid of pharmacological activity. Northern blot analysis demonstrated the expression of mMC5R mRNA in mouse skeletal muscle, lung, spleen, and brain.

Synthesis and Evaluation of Bivalent NDP-α-MSH(7) Peptide Ligands for Binding to the Human Melanocortin Receptor 4 (hMC4R)

“…The hMC4R vector was originally received from Dr. Ira Gantz, University of Michigan (19). The coding region of the hMC4R gene was expressed in pcDNA3.1 (Invitrogen, V790-20).…”

Structure–activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position

“…There are five known melanocortin receptor (MCR) subtypes, all of which belong to the family of seven transmembrane G-protein coupled receptors (GPCRs), and whose activation is linked to the generation of intracellular cAMP [3,7,8,12,[14][15][16]22,31,34,38]. Importantly, the interaction of the melanocortin peptides with their receptors can be modified by two endogenous protein antagonists, agouti, and agouti-related protein, which are the products of two distinct genes [33,35].…”

a-MSH enhances activity-based anorexia

“…The brain MC system comprises of (a) proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) and nucleus of the solitary tract [9,17]; (b) agouti-related protein (AGRP) neurons in the ARC [4,20] and (c) melanocortin 3 and 4 receptors (MCRs), which are widely distributed throughout the brain [16,36,39]. Stimulation of the MC system by intracerebroventricular (icv) infusion of a-melanocyte-stimulating hormone (a-MSH) or its analogs results in hypophagia [13,46].…”