melanocortin receptors

Summary

Summary: A family of G-protein-coupled receptors that have specificity for MELANOCYTE-STIMULATING HORMONES and ADRENOCORTICOTROPIC HORMONE. There are several subtypes of melanocortin receptors, each having a distinct ligand specificity profile and tissue localization.

Top Publications

  1. Logan D, Bryson Richardson R, Taylor M, Currie P, Jackson I. Sequence characterization of teleost fish melanocortin receptors. Ann N Y Acad Sci. 2003;994:319-30 pubmed
    ..By in silico analysis, we have identified the full complement of melanocortin receptors in both zebrafish and the pufferfish, FUGU: Mammals have five such receptors...
  2. Whitaker K, Reyes T. Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1beta administration. Neuropharmacology. 2008;54:509-20 pubmed
    ..Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1beta. ..
  3. Zhong Q, Sridhar S, Ruan L, Ding K, Xie D, Insogna K, et al. Multiple melanocortin receptors are expressed in bone cells. Bone. 2005;36:820-31 pubmed
    b>Melanocortin receptors belong to the seven transmembrane domain, G-protein coupled family of receptors. There are five members of this receptor family labeled MC1R-MC5R...
  4. Catania A, Gatti S, Colombo G, Lipton J. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol Rev. 2004;56:1-29 pubmed
    ..Recognition and cloning of five melanocortin receptors (MCRs) has greatly improved understanding of peptide-target cell interactions...
  5. 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. ..
  6. Schioth H, Haitina T, Fridmanis D, Klovins J. Unusual genomic structure: melanocortin receptors in Fugu. Ann N Y Acad Sci. 2005;1040:460-3 pubmed
    ..The MC2 and MC5 receptors in the pufferfish have introns. Moreover, these two receptors are found in a tandem that is remarkably conserved in several vertebrate species. Here, we speculate about the genomic origin of the MC receptors. ..
  7. Gantz I, Fong T. The melanocortin system. Am J Physiol Endocrinol Metab. 2003;284:E468-74 pubmed
    The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins...
  8. Holder J, Xiang Z, Bauzo R, Haskell Luevano C. Structure-activity relationships of the melanocortin tetrapeptide Ac-His-D-Phe-Arg-Trp-NH2 at the mouse melanocortin receptors. 4. Modifications at the Trp position. J Med Chem. 2002;45:5736-44 pubmed
    ..position (alpha-MSH numbering) and pharmacologically characterized for agonist activity at the mouse melanocortin receptors MC1R, MC3R, MC4R, and MC5R...
  9. Lapinsh M, Veiksina S, Uhlen S, Petrovska R, Mutule I, Mutulis F, et al. Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes. Mol Pharmacol. 2005;67:50-9 pubmed
    ..Proteochemometrics was applied in the analysis of the binding of organic compounds to wild-type and chimeric melanocortin receptors. Thirteen chimeric melanocortin receptors were designed based on statistical molecular design; each ..

More Information

Publications62

  1. Yang Y, Thompson D, Dickinson C, Wilken J, Barsh G, Kent S, et al. Characterization of Agouti-related protein binding to melanocortin receptors. Mol Endocrinol. 1999;13:148-55 pubmed
    ..sequence), in its ability to dose dependently inhibit alpha-MSH-generated cAMP generation at the cloned melanocortin receptors. Furthermore, deletion of the amino-terminal portion of the full-length variant did not alter the MCR ..
  2. Lapinsh M, Prusis P, Mutule I, Mutulis F, Wikberg J. QSAR and proteo-chemometric analysis of the interaction of a series of organic compounds with melanocortin receptor subtypes. J Med Chem. 2003;46:2572-9 pubmed
    ..71 for the MC(1), MC(3)(-)(5) receptor, respectively. However, the proteo-chemometrics modeling provided more detailed information about receptor-ligand interactions and determinants for receptor subtype selectivity than did QSAR. ..
  3. Cone R. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8:571-8 pubmed
    ..a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment ..
  4. Prusis P, Lundstedt T, Wikberg J. Proteo-chemometrics analysis of MSH peptide binding to melanocortin receptors. Protein Eng. 2002;15:305-11 pubmed
    ..melanocortins is located between the first, second, third, sixth and seventh transmembrane regions of the melanocortin receptors, in good agreement with previous three-dimensional models for the interactions of melanocortins with ..
  5. Jun D, Na K, Kim W, Kwak D, Kwon E, Yoon J, et al. Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptors 2 and 5 in 3T3-L1 adipocytes. J Mol Endocrinol. 2010;44:225-36 pubmed publisher
    ..Il6 gene expression and production in 3T3-L1 adipocytes through membrane receptors which are called melanocortin receptors (MCRs)...
  6. Haitina T, Klovins J, Schioth H. Pharmacological characterization of melanocortin receptors in fish suggests an important role for ACTH. Ann N Y Acad Sci. 2005;1040:337-9 pubmed
  7. Bednarek M, MacNeil T, Kalyani R, Tang R, Van der Ploeg L, Weinberg D. Analogs of MTII, lactam derivatives of alpha-melanotropin, modified at the N-terminus, and their selectivity at human melanocortin receptors 3, 4, and 5. Biochem Biophys Res Commun. 1999;261:209-13 pubmed
    ..at human melanocortin-4 receptor, proline-substituted analogs of MTII, a potent nonselective agonist at melanocortin receptors, were prepared by solid-phase syntheses and evaluated for their ability to bind and activate human MC-3, ..
  8. Dores R. Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: revisiting the work of Robert Schwyzer: a thirty-year retrospective. Ann N Y Acad Sci. 2009;1163:93-100 pubmed publisher
    ..on the interactions between adrenocorticotropic hormone and alpha-melanocyte-stimulating hormone and the melanocortin receptors. This mini review will evaluate how the predictions made in the 1977 review have held up and also propose ..
  9. Prusis P, Muceniece R, Andersson P, Post C, Lundstedt T, Wikberg J. PLS modeling of chimeric MS04/MSH-peptide and MC1/MC3-receptor interactions reveals a novel method for the analysis of ligand-receptor interactions. Biochim Biophys Acta. 2001;1544:350-7 pubmed
    ..Moreover, the cross-terms of the PLS model revealed the existence of a strong interaction between TM6/7 and TM2/3 of the receptors. ..
  10. Ringholm A, Fredriksson R, Poliakova N, Yan Y, Postlethwait J, Larhammar D, et al. One melanocortin 4 and two melanocortin 5 receptors from zebrafish show remarkable conservation in structure and pharmacology. J Neurochem. 2002;82:6-18 pubmed
  11. Minokoshi Y, Alquier T, Furukawa N, Kim Y, Lee A, Xue B, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428:569-74 pubmed
    ..Thus, hypothalamic AMPK plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance. ..
  12. Iwen K, Senyaman O, Schwartz A, Drenckhan M, Meier B, Hadaschik D, et al. Melanocortin crosstalk with adipose functions: ACTH directly induces insulin resistance, promotes a pro-inflammatory adipokine profile and stimulates UCP-1 in adipocytes. J Endocrinol. 2008;196:465-72 pubmed publisher
  13. Klovins J, Haitina T, Fridmanis D, Kilianova Z, Kapa I, Fredriksson R, et al. The melanocortin system in Fugu: determination of POMC/AGRP/MCR gene repertoire and synteny, as well as pharmacology and anatomical distribution of the MCRs. Mol Biol Evol. 2004;21:563-79 pubmed publisher
    The G-protein-coupled melanocortin receptors (MCRs) play an important role in a variety of essential functions such as the regulation of pigmentation, energy homeostasis, and steroid production...
  14. Skibicka K, Grill H. Energetic responses are triggered by caudal brainstem melanocortin receptor stimulation and mediated by local sympathetic effector circuits. Endocrinology. 2008;149:3605-16 pubmed publisher
    The central melanocortin system is a critical contributor to energy balance control. Melanocortin receptors (MC-Rs) are widely distributed throughout forebrain and caudal brainstem nuclei...
  15. Grossman H, Hadjimarkou M, Silva R, Giraudo S, Bodnar R. Interrelationships between mu opioid and melanocortin receptors in mediating food intake in rats. Brain Res. 2003;991:240-4 pubmed
    ..v.), especially at those intake periods (24-48 h) when SHU-9119 produced maximal ingestive effects. These data extend previous findings demonstrating interactions between opioid and melanocortin receptors in the mediation of food intake.
  16. Pierroz D, Ziotopoulou M, Ungsunan L, Moschos S, Flier J, Mantzoros C. Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Diabetes. 2002;51:1337-45 pubmed
    ..In conclusion, treatment with a melanocortin agonist is a promising therapeutic approach to DIO and associated insulin resistance. ..
  17. Grassel S, Opolka A, Anders S, Straub R, Grifka J, Luger T, et al. The melanocortin system in articular chondrocytes: melanocortin receptors, pro-opiomelanocortin, precursor proteases, and a regulatory effect of alpha-melanocyte-stimulating hormone on proinflammatory cytokines and extracellular matrix components. Arthritis Rheum. 2009;60:3017-27 pubmed publisher
  18. Cone R. Studies on the physiological functions of the melanocortin system. Endocr Rev. 2006;27:736-49 pubmed
    ..and paracrine signaling pathways that are defined by components that include the five G protein-coupled melanocortin receptors; peptide agonists derived from the proopiomelanocortin preprohormone precursor; and the endogenous ..
  19. Yang Y, Harmon C. Recent developments in our understanding of melanocortin system in the regulation of food intake. Obes Rev. 2003;4:239-48 pubmed
    ..of several components: (1) melanocortin peptides; (2) the five seven-transmembrane G-protein coupled melanocortin receptors (MCRs); (3) the endogenous MCR antagonists, agouti and agouti-related protein; (4) the endogenous ..
  20. 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. ..
  21. Gutierrez Juarez R, Obici S, Rossetti L. Melanocortin-independent effects of leptin on hepatic glucose fluxes. J Biol Chem. 2004;279:49704-15 pubmed
    ..We conclude that leptin regulates hepatic glucose fluxes through a melanocortin-dependent pathway leading to stimulation of gluconeogenesis and a melanocortin-independent pathway causing inhibition of GP and glycogenolysis. ..
  22. Haskell Luevano C, Holder J, Monck E, Bauzo R. Characterization of melanocortin NDP-MSH agonist peptide fragments at the mouse central and peripheral melanocortin receptors. J Med Chem. 2001;44:2247-52 pubmed
    The central melanocortin receptors, melanocortin-4 (MC4R) and melanocortin-3 (MC3R), are involved in the regulation of satiety and energy homeostasis...
  23. 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
  24. Boston B. The role of melanocortins in adipocyte function. Ann N Y Acad Sci. 1999;885:75-84 pubmed
    ..ACTH potently stimulates cyclase with EC50 values that are consistent with the hypothesis that the murine MC2 receptor, not the MC5 receptor, mediates stress-induced lipolysis via release of ACTH from the pituitary. ..
  25. Adan R, Szklarczyk A, Oosterom J, Brakkee J, Nijenhuis W, Schaaper W, et al. Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur J Pharmacol. 1999;378:249-58 pubmed
    ..Furthermore, blockade of novelty-induced grooming behavior by SHU9119 demonstrated that this physiological stress response is mediated via activation of the melanocortin system. ..
  26. Poritsanos N, Wong D, Vrontakis M, Mizuno T. Regulation of hepatic PPARgamma2 and lipogenic gene expression by melanocortin. Biochem Biophys Res Commun. 2008;376:384-8 pubmed publisher
    ..These findings suggest that reduced central melanocortin signaling increases hepatic lipid deposition by stimulating hepatic lipogenic gene expression at least partly through the activation of SREBP-1c and PPARgamma2. ..
  27. Skibicka K, Grill H. Hindbrain leptin stimulation induces anorexia and hyperthermia mediated by hindbrain melanocortin receptors. Endocrinology. 2009;150:1705-11 pubmed publisher
    ..b>Melanocortin receptors (MC-Rs) contribute to the feeding and energetic effects of hypothalamically delivered leptin...
  28. Abdel Malek Z, Scott M, Suzuki I, Tada A, Im S, Lamoreux L, et al. The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation. Pigment Cell Res. 2000;13 Suppl 8:156-62 pubmed
    ..These results begin to elucidate the significance of MC1R variants in the function of the receptor. Our data emphasize the significance of a normally functioning MC1R in the response of melanocytes to melanocortins, ASP, and UVR. ..
  29. Bohm M, Luger T, Tobin D, García Borrón J. Melanocortin receptor ligands: new horizons for skin biology and clinical dermatology. J Invest Dermatol. 2006;126:1966-75 pubmed
    ..These findings should improve our understanding of skin physiology and pathophysiology and may offer novel strategies with MCs as future therapeutics for skin diseases. ..
  30. Schioth H, Petersson S, Muceniece R, Szardenings M, Wikberg J. Deletions of the N-terminal regions of the human melanocortin receptors. FEBS Lett. 1997;410:223-8 pubmed
    ..The results indicate that the N-terminal regions of the human MC1, MC3, MC4 and MC5 receptors, do not play an important role for the ligand binding properties of these receptors. ..
  31. Chhajlani V. Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int. 1996;38:73-80 pubmed
  32. Fathi Z, Iben L, Parker E. Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype. Neurochem Res. 1995;20:107-13 pubmed
    ..Lower but detectable levels of MC5 mRNA are also found in RT2-2 retinal neuronal cells, lung, testis, spleen, heart, kidney, and liver. ..
  33. Prusis P, Schioth H, Muceniece R, Herzyk P, Afshar M, Hubbard R, et al. Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide. J Mol Graph Model. 1997;15:307-17, 334 pubmed
  34. Chen W, Kelly M, Opitz Araya X, Thomas R, Low M, Cone R. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell. 1997;91:789-98 pubmed
    ..These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides. ..
  35. Schioth H, Muceniece R, Mutulis F, Prusis P, Lindeberg G, Sharma S, et al. Selectivity of cyclic [D-Nal7] and [D-Phe7] substituted MSH analogues for the melanocortin receptor subtypes. Peptides. 1997;18:1009-13 pubmed
    ..However, the cyclic lactams displayed an over all higher affinity for the MC receptors, than any of the cyclic disulphide MSH (4-10) analogues. ..
  36. 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. ..
  37. Chagnon Y, Chen W, Perusse L, Chagnon M, Nadeau A, Wilkison W, et al. Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Québec Family Study. Mol Med. 1997;3:663-73 pubmed
    ..adrenergic tone arising from antagonizing alpha-melanocyte-stimulating hormone (MSH) activation of melanocortin receptors (MCR) could be at the origin of the obesity phenotype...
  38. Diamond L, Earle D, Rosen R, Willett M, Molinoff P. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot Res. 2004;16:51-9 pubmed
    ..Based upon its erectogenic potential and tolerability profile, PT-141 is a promising candidate for further evaluation as a treatment for male ED. ..
  39. Fotsch C, Smith D, Adams J, Cheetham J, Croghan M, Doherty E, et al. Design of a new peptidomimetic agonist for the melanocortin receptors based on the solution structure of the peptide ligand, Ac-Nle-cyclo[Asp-Pro-DPhe-Arg-Trp-Lys]-NH(2). Bioorg Med Chem Lett. 2003;13:2337-40 pubmed
    ..Subtle changes in cyclohexane stereochemistry and removal of functional groups led to analogues with lower affinity for the MC receptors. ..
  40. Xu L, Vagner J, Alleti R, Rao V, Jagadish B, Morse D, et al. Synthesis and characterization of a Eu-DTPA-PEGO-MSH(4) derivative for evaluation of binding of multivalent molecules to melanocortin receptors. Bioorg Med Chem Lett. 2010;20:2489-92 pubmed publisher
    ..While results from the latter assay reflected only statistical effects, results from the former assay reflected a mixture of statistical, proximity, and/or cooperative binding effects. ..
  41. Grützkau A, Henz B, Kirchhof L, Luger T, Artuc M. alpha-Melanocyte stimulating hormone acts as a selective inducer of secretory functions in human mast cells. Biochem Biophys Res Commun. 2000;278:14-9 pubmed
    ..These results suggest that alpha-MSH may selectively induce acute inflammatory effects via secretion of histamine. ..
  42. Mutch D, Clement K. Genetics of human obesity. Best Pract Res Clin Endocrinol Metab. 2006;20:647-64 pubmed
    ..It is now necessary to integrate data of various origins (environment, genotype, expression) to clarify this field. ..
  43. Asai M, Ramachandrappa S, Joachim M, Shen Y, Zhang R, Nuthalapati N, et al. Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity. Science. 2013;341:275-8 pubmed publisher
    Melanocortin receptor accessory proteins (MRAPs) modulate signaling of melanocortin receptors in vitro...
  44. Rusciano D, Lorenzoni P, Burger M. Regulation of c-met expression in B16 murine melanoma cells by melanocyte stimulating hormone. J Cell Sci. 1999;112 ( Pt 5):623-30 pubmed
  45. Adage T, Scheurink A, de Boer S, de Vries K, Konsman J, Kuipers F, et al. Hypothalamic, metabolic, and behavioral responses to pharmacological inhibition of CNS melanocortin signaling in rats. J Neurosci. 2001;21:3639-45 pubmed
    ..e., CART, POMC, and NPY) and paraventricular (i.e., CRH) hypothalamus. The results indicate that reduced activity of the CNS MC pathway promotes fat deposition via both food intake-dependent and -independent mechanisms. ..
  46. Rana B. New insights into G-protein-coupled receptor signaling from the melanocortin receptor system. Mol Pharmacol. 2003;64:1-4 pubmed
  47. Smith Thomas L, Moustafa M, Dawson R, Wagner M, Balafa C, Haycock J, et al. Cellular and hormonal regulation of pigmentation in human ocular melanocytes. Pigment Cell Res. 2001;14:298-309 pubmed
    ..These in vitro studies suggest that ocular melanocytes have the capacity to be influenced by adjacent epithelial and stromal cells with respect to pigmentation. ..
  48. Rana B, Hewett Emmett D, Jin L, Chang B, Sambuughin N, Lin M, et al. High polymorphism at the human melanocortin 1 receptor locus. Genetics. 1999;151:1547-57 pubmed
    ..In addition, the nucleotide diversity at the MC1R locus is shown to be several times higher than the average nucleotide diversity in human populations, possibly due to diversifying selection. ..
  49. Xing Y, Nakamura Y, Rainey W. G protein-coupled receptor expression in the adult and fetal adrenal glands. Mol Cell Endocrinol. 2009;300:43-50 pubmed publisher
    ..However, the exact function of GnRHR in fetal adrenal remains to be determined. ..
  50. Anderson E, Çakir I, Carrington S, Cone R, Ghamari Langroudi M, Gillyard T, et al. 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH. J Mol Endocrinol. 2016;56:T157-74 pubmed publisher
    ..Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the ..
  51. Gómez SanMiguel A, Villanúa M, Martín A, López Calderón A. D-TRP(8)-γMSH Prevents the Effects of Endotoxin in Rat Skeletal Muscle Cells through TNFα/NF-KB Signalling Pathway. PLoS ONE. 2016;11:e0155645 pubmed publisher
  52. Goodfellow V, Saunders J. The melanocortin system and its role in obesity and cachexia. Curr Top Med Chem. 2003;3:855-83 pubmed
    b>Melanocortin receptors (MC-R) activated by one of several peptides derived from the pro-opiomelanocortin (POMC) precursor have become leading contenders for a pivotal role in controlling food intake...
  53. Hruby V, Cai M, Grieco P, Han G, Kavarana M, Trivedi D. Exploring the stereostructural requirements of peptide ligands for the melanocortin receptors. Ann N Y Acad Sci. 2003;994:12-20 pubmed
    ..peptides alpha-MSH, gamma-MSH, and beta-MSH are believed to be the natural ligands for the four melanocortin receptors, MC1R, MC3R, MC4R, and MC5R. However, these peptides generally have low selectivity for these receptors...