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Gene Review

Mc3r  -  melanocortin 3 receptor

Rattus norvegicus

Synonyms: MC3-R, Melanocortin receptor 3
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Disease relevance of Mc3r

  • We conclude that the hypotension and bradycardia elicited by the release of alpha-MSH from arcuate neurons is mediated by neural melanocortin receptors (MC4-R/MC3-R) located in the DVC, whereas the similar effects of beta-endorphin, a peptide derived from the same precursor, are mediated by opiate receptors at the same site [1].
  • We have examined the effects of underfeeding and obesity on the density of hypothalamic melanocortin MC3 and MC4 receptors (MC3-R and MC4-R, respectively), which may mediate the hypophagic effects of alpha-melanocyte-stimulating hormone (MSH) in the rat [2].
  • 2. As was previously found by other investigators as well as by us gamma 2-MSH, a peptide suggested to be an agonist with selectivity for the melanocortin MC3 receptor, caused a dose-dependent, short lasting pressor response in combination with a tachycardia [3].

Psychiatry related information on Mc3r

  • Rats were fasted overnight to promote feeding behavior, then injected intraperitoneally with LPS (100 micrograms/kg ip), followed 30 min later by intracerebroventricular injection of either alpha-MSH or the melanocortin receptor subtype 3/subtype 4 (MC3-R/MC4-R) antagonist SHU-9119 [4].

High impact information on Mc3r


Biological context of Mc3r

  • Investigation of the melanocyte stimulating hormones on food intake. Lack Of evidence to support a role for the melanocortin-3-receptor [9].
  • NPY is orexigenic and decreases energy expenditure whereas alpha-MSH reduces food consumption and stimulates catabolism. alpha-MSH is an endogenous ligand for the central melanocortin receptors, MC3-R and MC4-R [10].
  • These studies therefore indicate a role for PKC isozymes in gamma-2-MSH/MC3-R receptor signaling and in neuronal cell differentiation [11].
  • These data suggest that the physiological roles of neural melanocortin receptors, MC3R and MC4R, are likely determined by distinct tissue distribution patterns and suggest a role for hypothalamic and intra-adrenal melanocortin systems in the manifestation of stress related pathologies [12].
  • These results indicate that reflex natriuresis after AUN is accompanied by an increase in plasma gamma-MSH but not ANP or oxytocin concentration and is prevented by intrarenal infusion of receptor antagonists with selectivity for MC3-R [13].

Anatomical context of Mc3r


Associations of Mc3r with chemical compounds

  • In addition, neither melanotan-II (1.0 nmol, a non-selective MC3/4-R agonist) nor gamma(1)-melanocyte-stimulating hormone (10 nmol, a selective MC3-R agonist) affected significantly GH release in fasted rats [18].
  • 4. These results imply that the melanocortin-4-receptor, and not the melanocortin-3-receptor, is involved in the ACTH1-24-induced rise in plasma levels of ACTH and corticosterone, and excessive grooming [19].
  • Detection of melanocortin-3 receptor mRNA in immature rat pituitary: functional relation to gamma3-MSH-induced changes in intracellular Ca2+ concentration [20]?
  • Central MC3-R/MC4-R blockade did not affect Tb or food intake in the absence of LPS treatment, but it reversed the LPS-induced reduction in 24-h food intake and increased LPS-induced fever without altering the LPS-induced suppression of locomotion [4].

Regulatory relationships of Mc3r

  • The proportion of POMC neurones expressing MC3-R mRNA was significantly higher in the most rostral (43.5%) than in the most posterior part of the arcuate nucleus (8.2%) [16].

Other interactions of Mc3r

  • We investigated endogenous melanocortin ligand binding and activation at the MC3-R and MC4-R and their effects on feeding [9].
  • RT-PCR of rat kidney RNA demonstrated reaction products of the expected size in both cortex and medulla for MC3-R, MC4-R, and MC5-R mRNA; no signal for MC1-R or MC2-R was detected [21].
  • The occurrence of MC3-R mRNA in POMC-positive cell bodies was demonstrated using a double-labelling in situ hybridization technique [16].

Analytical, diagnostic and therapeutic context of Mc3r

  • The effects of alpha-MSH are inhibited by microinjection to the same site of the novel MG4-R/MC3-R antagonist SHU9119 (2-100 pmol) but not naloxone (270 pmol), whereas the similar effects of intra-DVC injection of beta-endorphin (1 pmol) are inhibited by naloxone and not by SHU9119 [1].
  • MC3-R and MC4-R were measured by quantitative autoradiography in brain sections using 125I-labeled Nle4-D-Phe7-alpha-MSH (125I-NDP-MSH) and discriminated by masking MC3-R with excess unlabelled gamma2-MSH [2].
  • Finally, the melanocortin-3 receptor was detected in all examined cell types by Western blot [5].


  1. Melanocortin antagonists define two distinct pathways of cardiovascular control by alpha- and gamma-melanocyte-stimulating hormones. Li, S.J., Varga, K., Archer, P., Hruby, V.J., Sharma, S.D., Kesterson, R.A., Cone, R.D., Kunos, G. J. Neurosci. (1996) [Pubmed]
  2. Altered energy balance causes selective changes in melanocortin-4(MC4-R), but not melanocortin-3 (MC3-R), receptors in specific hypothalamic regions: further evidence that activation of MC4-R is a physiological inhibitor of feeding. Harrold, J.A., Widdowson, P.S., Williams, G. Diabetes (1999) [Pubmed]
  3. Different cardiovascular profiles of three melanocortins in conscious rats; evidence for antagonism between gamma 2-MSH and ACTH-(1-24). Van Bergen, P., Kleijne, J.A., De Wildt, D.J., Versteeg, D.H. Br. J. Pharmacol. (1997) [Pubmed]
  4. Role of central melanocortins in endotoxin-induced anorexia. Huang, Q.H., Hruby, V.J., Tatro, J.B. Am. J. Physiol. (1999) [Pubmed]
  5. ACTH enhances chondrogenesis in multipotential progenitor cells and matrix production in chondrocytes. Evans, J.F., Niu, Q.T., Canas, J.A., Shen, C.L., Aloia, J.F., Yeh, J.K. Bone (2004) [Pubmed]
  6. Melanocortin-4 receptor messenger RNA expression is up-regulated in the non-damaged striatum following unilateral hypoxic-ischaemic brain injury. Mountjoy, K.G., Guan, J., Elia, C.J., Sirimanne, E.S., Williams, C.E. Neuroscience (1999) [Pubmed]
  7. Postnatal expression of melanocortin-3 receptor in rat diencephalon and mesencephalon. Xia, Y., Wikberg, J.E. Neuropharmacology (1997) [Pubmed]
  8. Evidence that the effect of melanocortins on female sexual behavior in preoptic area is mediated by the MC3 receptor; Participation of nitric oxide. Nocetto, C., Cragnolini, A.B., Schiöth, H.B., Scimonelli, T.N. Behav. Brain Res. (2004) [Pubmed]
  9. Investigation of the melanocyte stimulating hormones on food intake. Lack Of evidence to support a role for the melanocortin-3-receptor. Abbott, C.R., Rossi, M., Kim, M., AlAhmed, S.H., Taylor, G.M., Ghatei, M.A., Smith, D.M., Bloom, S.R. Brain Res. (2000) [Pubmed]
  10. Expression of Melanocortin MC3 and MC4 Receptor mRNAs by Neuropeptide Y Neurons in the Rat Arcuate Nucleus. Mounien, L., Bizet, P., Boutelet, I., Vaudry, H., Jégou, S. Neuroendocrinology (2005) [Pubmed]
  11. Evidence for the interaction of protein kinase C and melanocortin 3-receptor signaling pathways. Wachira, S.J., Hughes-Darden, C.A., Taylor, C.V., Ochillo, R., Robinson, T.J. Neuropeptides (2003) [Pubmed]
  12. Neural melanocortin receptors are differentially expressed and regulated by stress in rat hypothalamic-pituitary-adrenal axis. Wachira, S.J., Hughes-Darden, C.A., Nicholas, H.B., Taylor, C.V., Robinson, T.J. Cell. Mol. Biol. (Noisy-le-grand) (2004) [Pubmed]
  13. Prevention of reflex natriuresis after acute unilateral nephrectomy by melanocortin receptor antagonists. Ni, X.P., Kesterson, R.A., Sharma, S.D., Hruby, V.J., Cone, R.D., Wiedemann, E., Humphreys, M.H. Am. J. Physiol. (1998) [Pubmed]
  14. Different developmental patterns of melanocortin MC3 and MC4 receptor mRNA: predominance of Mc4 in fetal rat nervous system. Kistler-Heer, V., Lauber, M.E., Lichtensteiger, W. J. Neuroendocrinol. (1998) [Pubmed]
  15. Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. Bagnol, D., Lu, X.Y., Kaelin, C.B., Day, H.E., Ollmann, M., Gantz, I., Akil, H., Barsh, G.S., Watson, S.J. J. Neurosci. (1999) [Pubmed]
  16. Melanocortin-3 receptor mRNA expression in pro-opiomelanocortin neurones of the rat arcuate nucleus. Jégou, S., Boutelet, I., Vaudry, H. J. Neuroendocrinol. (2000) [Pubmed]
  17. Characterization of the neuroanatomical distribution of agouti-related protein immunoreactivity in the rhesus monkey and the rat. Haskell-Luevano, C., Chen, P., Li, C., Chang, K., Smith, M.S., Cameron, J.L., Cone, R.D. Endocrinology (1999) [Pubmed]
  18. Evaluation of the role of melanocortin 3 and 4 receptors in leptin-stimulated and spontaneous growth hormone secretion in rats. Watanobe, H., Yoneda, M. Neuroendocrinology (2003) [Pubmed]
  19. The role of central melanocortin receptors in the activation of the hypothalamus-pituitary-adrenal-axis and the induction of excessive grooming. Von Frijtag, J.C., Croiset, G., Gispen, W.H., Adan, R.A., Wiegant, V.M. Br. J. Pharmacol. (1998) [Pubmed]
  20. Detection of melanocortin-3 receptor mRNA in immature rat pituitary: functional relation to gamma3-MSH-induced changes in intracellular Ca2+ concentration? Lorsignol, A., Vande Vijver, V., Ramaekers, D., Vankelecom, H., Denef, C. J. Neuroendocrinol. (1999) [Pubmed]
  21. Modulation by dietary sodium intake of melanocortin 3 receptor mRNA and protein abundance in the rat kidney. Ni, X.P., Bhargava, A., Pearce, D., Humphreys, M.H. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
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