Gene Symbol: Mc3r
Description: melanocortin 3 receptor
Alias: melanocortin receptor 3, MC3-R
Species: rat
Products:     Mc3r

Top Publications

  1. Catania A, Lonati C, Sordi A, Carlin A, Leonardi P, Gatti S. The melanocortin system in control of inflammation. ScientificWorldJournal. 2010;10:1840-53 pubmed publisher
    ..This review examines the main signaling circuits in anti-inflammatory and immunomodulatory actions of melanocortins, and the potential therapeutic use of these molecules. ..
  2. Roselli Rehfuss L, Mountjoy K, Robbins L, Mortrud M, Low M, Tatro J, et al. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci U S A. 1993;90:8856-60 pubmed
    ..The location and properties of this receptor provide a pharmacological basis for the action of POMC peptides produced in the brain and possibly a specific physiological role for gamma-MSH. ..
  3. Williams D, Bowers R, Bartness T, Kaplan J, Grill H. Brainstem melanocortin 3/4 receptor stimulation increases uncoupling protein gene expression in brown fat. Endocrinology. 2003;144:4692-7 pubmed
  4. da Silva A, do Carmo J, Kanyicska B, Dubinion J, Brandon E, Hall J. Endogenous melanocortin system activity contributes to the elevated arterial pressure in spontaneously hypertensive rats. Hypertension. 2008;51:884-90 pubmed publisher
    ..These results also support the hypothesis that weight gain does not raise arterial pressure in the absence of a functional MC3/4-R. ..
  5. Lawrence C, Liu Y, Stock M, Luckman S. Anorectic actions of prolactin-releasing peptide are mediated by corticotropin-releasing hormone receptors. Am J Physiol Regul Integr Comp Physiol. 2004;286:R101-7 pubmed
    ..These results show that the anorectic actions of PrRP are mediated by central CRH receptors but not by melanocortin receptors-3/4 and that PrRP can modify Vo2. ..
  6. Chan L, Webb T, Chung T, Meimaridou E, Cooray S, Guasti L, et al. MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc Natl Acad Sci U S A. 2009;106:6146-51 pubmed publisher
    ..MC2R is a critical component of the hypothalamic-pituitary-adrenal axis, whereas MC3R and MC4R have an essential role in energy homeostasis...
    ..and 5-HT1BR on their thyroid status is a strong argument in favor of participation of these receptors and intracellular signaling pathways associated with them in the regulation of HPT axis. ..
  8. Lindqvist N, Näpänkangas U, Lindblom J, Hallböök F. Proopiomelanocortin and melanocortin receptors in the adult rat retino-tectal system and their regulation after optic nerve transection. Eur J Pharmacol. 2003;482:85-94 pubmed
    ..Together, these data implicate a role for the melanocortin system in the adult rat retina and that melanocortins can stimulate neurite growth from retinal neurons. ..
  9. Getting S, Lam C, Chen A, Grieco P, Perretti M. Melanocortin 3 receptors control crystal-induced inflammation. FASEB J. 2006;20:2234-41 pubmed
    ..In conclusion, using an integrated transgenic and pharmacological approach, we provide strong proof of concept for the development of selective MC3-R agonists as novel anti-inflammatory therapeutics. ..

More Information


  1. Silva A, Kuo J, Tallam L, Liu J, Hall J. Does obesity induce resistance to the long-term cardiovascular and metabolic actions of melanocortin 3/4 receptor activation?. Hypertension. 2006;47:259-64 pubmed
    ..Thus, the metabolic and cardiovascular actions of chronic MC3/4-R activation are preserved in diet-induced obesity, supporting a potential role for the hypothalamic melanocortin system in obesity hypertension. ..
  2. Tavares E, Maldonado R, Minano F. Aminoprocalcitonin-mediated suppression of feeding involves the hypothalamic melanocortin system. Am J Physiol Endocrinol Metab. 2013;304:E1251-62 pubmed publisher
    ..These data demonstrate that hypothalamic N-PCT is involved in control of energy balance and that its anorexigenic effects are mediated through the melanocortin system. ..
  3. Irani B, Dunn Meynell A, Levin B. Altered hypothalamic leptin, insulin, and melanocortin binding associated with moderate-fat diet and predisposition to obesity. Endocrinology. 2007;148:310-6 pubmed
    ..These results corroborate our previous findings demonstrating a preexisting decrease in DIO hypothalamic leptin and insulin signaling and demonstrate that HE diet intake reduces hypothalamic melanocortin and hippocampal insulin binding. ..
  4. Kim M, Small C, Russell S, Morgan D, Abbott C, alAhmed S, et al. Effects of melanocortin receptor ligands on thyrotropin-releasing hormone release: evidence for the differential roles of melanocortin 3 and 4 receptors. J Neuroendocrinol. 2002;14:276-82 pubmed
    ..These data suggest differential roles for the MC3 and MC4 receptors in TRH release; MC3-R agonism inhibiting and MC4-R agonism stimulating TRH release. ..
  5. Daniels D, Suzuki A, Shapiro E, Luo L, Yee D, Fluharty S. Rattus norvegicus melanocortin 3 receptor: a corrected sequence. Peptides. 2005;26:1835-41 pubmed
    Examination of the Rattus norvegicus genome reveals differences in the melanocortin 3 receptor (MC3R) compared with the published sequence (accession X70667)...
  6. Skibicka K, Grill H. Hypothalamic and hindbrain melanocortin receptors contribute to the feeding, thermogenic, and cardiovascular action of melanocortins. Endocrinology. 2009;150:5351-61 pubmed publisher
    ..Data are consistent with the view that energetic and feeding responses are not controlled by regionally divergent MC3/4Rs and can be elicited from multiple, anatomically distributed MC3/4R populations. ..
  7. Feng N, Young S, Aguilera G, Puricelli E, Adler Wailes D, Sebring N, et al. Co-occurrence of two partially inactivating polymorphisms of MC3R is associated with pediatric-onset obesity. Diabetes. 2005;54:2663-7 pubmed
    Both human linkage studies and MC3R knockout mouse models suggest that the MC3R may play an important role in energy homeostasis. Here we show that among 355 overweight and nonoverweight children, 8...
  8. da Silva A, Kuo J, Hall J. Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin. Hypertension. 2004;43:1312-7 pubmed
    ..Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin. ..
  9. Li P, Cui B, Zhang L, Sun H, Liu T, Zhu G. Melanocortin 3/4 receptors in paraventricular nucleus modulate sympathetic outflow and blood pressure. Exp Physiol. 2013;98:435-43 pubmed publisher
    ..Melanocortin 3 receptors in the PVN may exert a tonic excitatory effect on sympathetic activity. ..
  10. Watanobe H, Yoneda M. Evaluation of the role of melanocortin 3 and 4 receptors in leptin-stimulated and spontaneous growth hormone secretion in rats. Neuroendocrinology. 2003;78:331-8 pubmed
  11. Wachira S, Guruswamy B, Uradu L, Hughes Darden C, Denaro F. Activation and endocytic internalization of melanocortin 3 receptor in neuronal cells. Ann N Y Acad Sci. 2007;1096:271-86 pubmed
    ..Studies with gene knockout mice have implicated neural melanocortin receptors, MC3R and MC4R, in the etiology of obesity, insulin resistance, and salt-sensitive hypertension...
  12. Wachira S, Temoney S, Ramlochansingh C, Hughes Darden C. Prevalence of melanocortin system transcripts in rat salt homeostasis endocrine tissues. Cell Mol Biol (Noisy-le-grand). 2007;53:8-14 pubmed
    ..POMC), POMC processing enzymes prohormone convertases 1 and 2 (PC1/PC2), melanocortin 3 receptor (MC3R) and melanocortin 5 receptor (MC5R) were not significantly affected by high dietary salt intake in either WKY or SP-..
  13. Peter J, Zipfel G, Lecourt A, Bekel A, Hofbauer K. Antibodies raised against different extracellular loops of the melanocortin-3 receptor affect energy balance and autonomic function in rats. J Recept Signal Transduct Res. 2010;30:444-53 pubmed publisher immunization against peptide sequences from the first and the third extracellular loop (EL1 and EL3) of the MC3R to generate selective antibodies (Abs) against this MCR subtype in rats...
  14. Shukla C, Britton S, Koch L, Novak C. Region-specific differences in brain melanocortin receptors in rats of the lean phenotype. Neuroreport. 2012;23:596-600 pubmed publisher
    ..Mutations and polymorphisms in MC3R and MC4R have been identified as one of the most common genetic contributors to obesity in human studies...
  15. Sutton G, Perez Tilve D, Nogueiras R, Fang J, Kim J, Cone R, et al. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci. 2008;28:12946-55 pubmed publisher
    ..Food anticipatory activity was assessed in wild-type (WT) and melanocortin-3 receptor-deficient (Mc3r-/-) C57BL/J mice by wheel running, spontaneous locomotory movement, and measurement of wakefulness...
  16. Kiefer L, Veal J, Mountjoy K, Wilkison W. Melanocortin receptor binding determinants in the agouti protein. Biochemistry. 1998;37:991-7 pubmed
    ..These agouti variants with altered receptor selectivity may be useful in determining the role of melanocortin receptors in diabetes and obesity. ..
  17. Yang Y, Hruby V, Chen M, Crasto C, Cai M, Harmon C. Novel binding motif of ACTH analogues at the melanocortin receptors. Biochemistry. 2009;48:9775-84 pubmed publisher
    ..Alpha-MSH and ACTH are endogenous nonselective agonists for MC1R, MC3R, MC4R, and MC5R...
  18. Harmer S, Bicknell A. The role of the melanocortin 3 receptor in mediating the effects of gamma-MSH peptides on the adrenal. Endocr Res. 2004;30:629-35 pubmed
    ..These results suggest that the MC3-R is not involved in mediating the potentiation effect, adding further evidence to the argument that another melanocortin receptor exists. ..
  19. Chandramohan G, Durham N, Sinha S, Norris K, Vaziri N. Role of gamma melanocyte-stimulating hormone-renal melanocortin 3 receptor system in blood pressure regulation in salt-resistant and salt-sensitive rats. Metabolism. 2009;58:1424-9 pubmed publisher
    ..Thus, the data suggest that gammaMSH-renal MC3-R pathway is activated and appears to be biologically functional in the DSS rats. ..
  20. Wachira S, Hughes Darden C, Taylor C, Ochillo R, Robinson T. Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways. Neuropeptides. 2003;37:201-10 pubmed
    ..However, the levels of classical PKC isozymes, PKC-alpha, PKC-gamma, and PKC-beta were unchanged. These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation. ..
  21. Lee Y, Poh L, Loke K. A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity. J Clin Endocrinol Metab. 2002;87:1423-6 pubmed
    The melanocortin 3 receptor (MC3R) plays a critical role in weight regulation as demonstrated in mouse models. We describe a novel mutation Ile183Asn (T548A) found in heterozygosity in a 13-year-old obese girl and her father...
  22. Pandit R, Omrani A, Luijendijk M, de Vrind V, van Rozen A, Ophuis R, et al. Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. Neuropsychopharmacology. 2016;41:2241-51 pubmed publisher
    The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R)...
  23. Ni X, Bhargava A, Pearce D, Humphreys M. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Am J Physiol Regul Integr Comp Physiol. 2006;290:R560-7 pubmed
    ..Because MC3-R is the receptor with which gamma-MSH interacts, our findings suggest the existence of a sodium-regulating system, activated in response to a HSD, which increases urinary sodium excretion to balance the high-sodium intake...
  24. Malik I, Triebel J, Posselt J, Khan S, Ramadori P, Raddatz D, et al. Melanocortin receptors in rat liver cells: change of gene expression and intracellular localization during acute-phase response. Histochem Cell Biol. 2012;137:279-91 pubmed publisher
    ..showed MC4R in the cytoplasm, but also in the nucleus of parenchymal and non-parenchymal liver cells, whereas MC3R-positivity was mainly cytoplasmic...
  25. Kim C, Lee S, Kim R, Kim B, Li S, Lee I, et al. Identification of domains directing specificity of coupling to G-proteins for the melanocortin MC3 and MC4 receptors. J Biol Chem. 2002;277:31310-7 pubmed
    The melanocortin receptors, MC3R and MC4R, are G protein-coupled receptors that are involved in regulating energy homeostasis...
  26. de Rijke C, Jackson P, Garner K, van Rozen R, Douglas N, Kas M, et al. Functional analysis of the Ala67Thr polymorphism in agouti related protein associated with anorexia nervosa and leanness. Biochem Pharmacol. 2005;70:308-16 pubmed
    ..Taken together, no evidence was found for a functional defect of Thr67 AgRP related to MC4R interactions. ..
  27. Dhillo W, Small C, Gardiner J, Bewick G, Whitworth E, Jethwa P, et al. Agouti-related protein has an inhibitory paracrine role in the rat adrenal gland. Biochem Biophys Res Commun. 2003;301:102-7 pubmed
    ..Our findings demonstrate that adrenal AgRP mRNA is regulated by glucocorticoids. AgRP acting via the MC3-R or MC4-R may have an inhibitory paracrine role, blocking alpha-MSH-induced corticosterone secretion. ..