CDB15:0001243 POMC — MC5R
Experimentally validated in Human, Mixed species; Orthology-inferred in Human, Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Sheep
Title
Journal:; Year Published:
Abstract
Ligand-dependent activation of the melanocortin 5 receptor: cAMP production and ryanodine receptor-dependent elevations of [Ca(2+)](I).
Biochemical and biophysical research communications, 2002; PubMed, Homo sapiens POMC — Mus Musculus Mc5r
ABSTRACT: The melanocortins are involved in the regulation of various cognitive and physiological processes such as learning, feeding, immune suppression, pigmentation, and sebum production. Five melanocortin receptors have been identified, of which the melanocortin 5 receptor (MC5R) has the most widespread distribution. This subtype is found in the brain, and at numerous peripheral sites including the skin where it is expressed in the sebaceous glands. The purpose of this study was to identify the peptide that functions as a natural ligand at the MC5R in the skin. alpha-MSH, ACTH1-39, ACTH1-17, ACTH1-10, and ACTH4-10 all increased the production of cAMP in HEK293 cells transfected with the mouse MC5R. alpha-MSH and ACTH1-17 were the most potent in this respect. In addition, all peptides stimulated a rapid and transient increase in [Ca(2+)](i), and, ACTH1-10 was the most potent. The increases in [Ca(2+)](i) were of intracellular origin, but not associated with inositol phosphate production. The elevations in [Ca(2+)](i) were reduced by ruthenium red and procaine and it is therefore possible that they were mediated via ryanodine receptors.
Characterisation of melanocortin receptor subtypes by radioligand binding analysis.
European journal of pharmacology, 1995; PubMed, Homo sapiens POMC — Homo sapiens MC5R
ABSTRACT: The DNAs encoding three melanocortin receptor subtypes (melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC5 receptor) were expressed individually in COS (CV-1 Origin, SV40) cells to characterise their ligand binding properties. The results indicated that [125I][Nle4, D-Phe7]alpha-MSH (melanocyte stimulating hormone) bound to a single saturable site with Kd values of 85.1 +/- 8.0 pmol/l (mean +/- S.E.M), 396 +/- 65 pmol/l and 5.05 +/- 1.00 nmol/l for melanocortin MC1 receptor, melanocortin MC3 receptor and melanocortin MC3 receptor, respectively. The melanocortin MC1 receptor and the melanocortin MC5 receptor showed a similar potency order to the melanocortic peptides examined which was markedly different from the potency order of the melanocortin MC3 receptor. The melanocortin MC1 receptor and melanocortin MC5 receptor had a relatively higher affinity for alpha-MSH than gamma-MSH and beta-MSH, whereas the melanocortin MC3 receptor had higher affinity for desacetyl-alpha-MSH, gamma-MSH and beta-MSH compared to alpha-MSH. The inclusion of the endopeptidase inhibitor phosphoramidon to prevent the breakdown of ACTH-(1-39) (adrenocorticotrophic hormone) to alpha-MSH, decreased ACTH-(1-39) binding affinity showing that ACTH-(1-39) had a much lower affinity for melanocortin MC1 receptor than reported earlier.
Molecular cloning, expression, and characterization of a fifth melanocortin receptor.
Biochemical and biophysical research communications, 1994; PubMed, Homo sapiens POMC — Mus Musculus Mc5r
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.