BPS/IUPHAR Guide to Pharmacology | GRAC GPCR FAMILIES

Melanocortin receptors

More information on this family may be found on the IUPHAR-DB family and introduction pages.

Melanocortin receptors (provisional nomenclature, [4]) are activated by members of the melanocortin family (α-MSH, β-MSH and γ-MSH forms; –δ form is not found in mammals) and adrenocorticotrophin (ACTH). Endogenous antagonists include agouti and agouti-related protein (AGRP).

Unless otherwise stated all data refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Receptors

MC₁ receptor Show »« Hide

Nomenclature

MC₁ receptor

Other names

MC1R, MSH-R, LOC292083, Mc1r_predicted, melanocortin 1 receptor (predicted), Mshra, extension recessive yellow, Tob

IUPHAR-DB

MC₁ receptor

Genes

MC1R (Hs), Mc1r (Mm), Mc1r (Rn)

Ensembl ID

ENSG00000258839 (Hs), ENSMUSG00000074037 (Mm)

Principal transduction

G_s

Rank order of potency

α-MSH > β-MSH > ACTH, γ-MSH

Radioligands
(K_d)

[¹²⁵I]NDP-MSH (Agonist, Full agonist) (3.3x10^-10 M) [6]

MC₂ receptor Show »« Hide

MC₃ receptor Show »« Hide

MC₄ receptor Show »« Hide

MC₅ receptor Show »« Hide

Comments Show »« Hide

Further Reading Show »« Hide

Breit, A; Büch, TR; Boekhoff, I; Solinski, HJ; Damm, E; Gudermann, T. (2011) Alternative G protein coupling and biased agonism: new insights into melanocortin-4 receptor signalling. Mol. Cell. Endocrinol., 331 (2): 232-40. [PMID:20674667]

Catania, A. (2007) The melanocortin system in leukocyte biology. J. Leukoc. Biol., 81 (2): 383-92. [PMID:17041004]

Cooray, SN; Clark, AJ. (2011) Melanocortin receptors and their accessory proteins. Mol. Cell. Endocrinol., 331 (2): 215-21. [PMID:20654690]

Ducrest, AL; Keller, L; Roulin, A. (2008) Pleiotropy in the melanocortin system, coloration and behavioural syndromes. Trends Ecol. Evol. (Amst.), 23 (9): 502-10. [PMID:18644658]

Farooqi, IS; O'Rahilly, S. (2008) Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab, 4 (10): 569-77. [PMID:18779842]

Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]

Greenfield, JR. (2011) Melanocortin signalling and the regulation of blood pressure in human obesity. J. Neuroendocrinol., 23 (2): 186-93. [PMID:21062377]

Mountjoy, KG. (2010) Functions for pro-opiomelanocortin-derived peptides in obesity and diabetes. Biochem. J., 428 (3): 305-24. [PMID:20504281]

Wikberg, JE; Mutulis, F. (2008) Targeting melanocortin receptors: an approach to treat weight disorders and sexual dysfunction. Nat Rev Drug Discov, 7 (4): 307-23. [PMID:18323849]

References Show »« Hide

1. Bednarek, M. A., MacNeil, T., Kalyani, R. N., Tang, R., Van der Ploeg, L. H. and Weinberg, D. H. (2001) Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. . J Med Chem., 44: 3665-3672. [PMID:11606131]

2. Chagnon, YC; Chen, WJ; Pérusse, L; Chagnon, M; Nadeau, A; Wilkison, WO; Bouchard, C. (1997) Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study. Mol. Med., 3 (10): 663-73. [PMID:9392003]

3. Farooqi, IS; O'Rahilly, S. (2008) Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab, 4 (10): 569-77. [PMID:18779842]

4. Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., Spedding, M. and Harmar, A. J. (2005) International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacol Rev, 57: 279-288. [PMID:15914470]

5. Grieco, P., Balse, P. M., Weinberg, D., MacNeil, T. and Hruby, V. J. (2000) D-Amino acid scan of γ-melanocyte-stimulating hormone: importance of Trp(8) on human MC₃ receptor selectivity. J. Med. Chem., 43: 4998-5002. [PMID:11150170]

6. Kopanchuk, S., Veiksina, S., Petrovska, R., Mutule, I., Szardenings, M., Rinken, A. and Wikberg, J. E. (2005) Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites. Eur J Pharmacol, 512: 85-95. [PMID:15840392]

7. Krishna, R; Gumbiner, B; Stevens, C; Musser, B; Mallick, M; Suryawanshi, S; Maganti, L; Zhu, H; Han, TH; Scherer, L; et al.. (2009) Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy. Clin. Pharmacol. Ther., 86 (6): 659-66. [PMID:19741604]

8. Nickolls, SA; Cismowski, MI; Wang, X; Wolff, M; Conlon, PJ; Maki, RA. (2003) Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity. J. Pharmacol. Exp. Ther., 304 (3): 1217-27. [PMID:12604699]

9. Schioth, H. B., Muceniece, R., Wikberg, J. E. and Chhajlani, V. (1995) Characterisation of the melanocortin 4 receptor by radioligand binding. Eur J Pharmacol, 288: 311-317. [PMID:7774675]

10. Schiöth, HB; Mutulis, F; Muceniece, R; Prusis, P; Wikberg, JE. (1998) Discovery of novel melanocortin4 receptor selective MSH analogues. Br. J. Pharmacol., 124 (1): 75-82. [PMID:9630346]

11. Sebhat, I. K., Martin, W. J., Ye, Z., Barakat, K., Mosley, R. T., Johnston, D. B., Bakshi, R., Palucki, B., Weinberg, D. H., MacNeil, T., Kalyani, R. N., Tang, R., Stearns, R. A., Miller, R. R., Tamvakopoulos, C., Strack, A. M., McGowan, E., Cashen, D. E., Drisko, J. E., Hom, G. J., Howard, A. D., MacIntyre, D. E., van der Ploeg, L. H., Patchett, A. A. and Nargund, R. P. (2002) Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J. Med. Chem. , 45: 4589-4593. [PMID:12361385]