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Melanocortin receptor

April 10, 2024

Melanocortin receptors are members of the rhodopsin family of 7-transmembrane G protein-coupled receptors.

There are five known members of the melanocortin receptor system[1] each with differing specificities for melanocortins:[2][3][4]

  • MC1R. MC1R is associated with pigmentation genetics.
  • MC2R. MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone.
  • MC3R. MC3R is associated with childhood growth, accrual of lean mass and onset of puberty.[5]
  • MC4R. Defects in MC4R are a cause of autosomal dominant obesity, accounting for 6% of all cases of early-onset obesity.[6]
  • MC5R. MC5R

These receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti-related peptide,[7] and activated by synthetic (i.e. afamelanotide) and endogenous agonist melanocyte-stimulating hormones.[8]

Selective ligands edit

Several selective ligands for the melanocortin receptors are known,[9][10][11][12] and some synthetic compounds have been investigated as potential tanning, anti-obesity and aphrodisiac drugs, with tanning effects mainly from stimulation of MC1,[13] while anorectic and aphrodisiac effects appear to involve both MC3 and MC4.[14] MC1, MC3 and MC4 are widely expressed in the brain, and are also thought to be responsible for effects on mood and cognition.[15][16][17][18]

Agonists edit

Non-selective
MC1-selective
MC4-selective
Unknown (but for certain MC2-acting)

Antagonists and inverse agonists edit

Non-selective
MC4-selective
  • HS-014
  • HS-024
  • MCL-0042[19]
  • MCL-0129[20]
  • MPB-10
  • SHU-9119 (agonist at MC1 and MC5, antagonist at MC3 and MC4)

Unknown edit

References edit

  1. ^ . Archived from the original on 2007-04-11. Retrieved 2007-03-14.
  2. ^ Voisey J, Carroll L, van Daal A (October 2003). "Melanocortins and their receptors and antagonists". Current Drug Targets. 4 (7): 586–97. doi:10.2174/1389450033490858. PMID 14535656.
  3. ^ Hadley ME, Dorr RT (April 2006). "Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization". Peptides. 27 (4): 921–30. doi:10.1016/j.peptides.2005.01.029. PMID 16412534.
  4. ^ Dores RM (April 2009). "Adrenocorticotropic hormone, melanocyte-stimulating hormone, and the melanocortin receptors: revisiting the work of Robert Schwyzer: a thirty-year retrospective". Annals of the New York Academy of Sciences. 1163 (1): 93–100. doi:10.1111/j.1749-6632.2009.04434.x. PMID 19456331.
  5. ^ Lam, B.Y.H., Williamson, A., Finer, S. et al. MC3R links nutritional state to childhood growth and the timing of puberty. Nature (2021). doi:10.1038/s41586-021-04088-9
  6. ^ Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S (2003). "Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene". N. Engl. J. Med. 348 (12): 1085–95. doi:10.1056/NEJMoa022050. PMID 12646665.
  7. ^ Chai B, Pogozheva I, Lai Y, Li J, Neubig R, Mosberg H, Gantz I (2005). "Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors". Biochemistry. 44 (9): 3418–31. doi:10.1021/bi0478704. PMID 15736952.
  8. ^ Pogozheva I, Chai B, Lomize A, Fong T, Weinberg D, Nargund R, Mulholland M, Gantz I, Mosberg H (2005). "Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists". Biochemistry. 44 (34): 11329–41. doi:10.1021/bi0501840. PMC 2532597. PMID 16114870.
  9. ^ Balse-Srinivasan P, Grieco P, Cai M, Trivedi D, Hruby VJ (November 2003). "Structure-activity relationships of gamma-MSH analogues at the human melanocortin MC3, MC4, and MC5 receptors. Discovery of highly selective hMC3R, hMC4R, and hMC5R analogues". Journal of Medicinal Chemistry. 46 (23): 4965–73. doi:10.1021/jm030119t. PMID 14584947.
  10. ^ Wilson KR, Todorovic A, Proneth B, Haskell-Luevano C (2006). "Overview of endogenous and synthetic melanocortin peptides". Cellular and Molecular Biology (Noisy-le-Grand, France). 52 (2): 3–20. PMID 16914082.
  11. ^ Hruby VJ, Cai M, Cain JP, Mayorov AV, Dedek MM, Trivedi D (2007). "Design, synthesis and biological evaluation of ligands selective for the melanocortin-3 receptor". Current Topics in Medicinal Chemistry. 7 (11): 1107–19. doi:10.2174/156802607780906645. PMC 2274922. PMID 17584128.
  12. ^ Mayorov AV, Cai M, Palmer ES, Dedek MM, Cain JP, Van Scoy AR, Tan B, Vagner J, Trivedi D, Hruby VJ (January 2008). "Structure-activity relationships of cyclic lactam analogues of alpha-melanocyte-stimulating hormone (alpha-MSH) targeting the human melanocortin-3 receptor". Journal of Medicinal Chemistry. 51 (2): 187–95. doi:10.1021/jm070461w. PMC 2587288. PMID 18088090.
  13. ^ Kadekaro AL, Kanto H, Kavanagh R, Abdel-Malek ZA (June 2003). "Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation, proliferation, and survival". Annals of the New York Academy of Sciences. 994 (1): 359–65. doi:10.1111/j.1749-6632.2003.tb03200.x. PMID 12851336.
  14. ^ King SH, Mayorov AV, Balse-Srinivasan P, Hruby VJ, Vanderah TW, Wessells H (2007). "Melanocortin receptors, melanotropic peptides and penile erection". Current Topics in Medicinal Chemistry. 7 (11): 1098–1106. doi:10.2174/1568026610707011111. PMC 2694735. PMID 17584130.
  15. ^ Cragnolini AB, Schiöth HB, Scimonelli TN (June 2006). "Anxiety-like behavior induced by IL-1beta is modulated by alpha-MSH through central melanocortin-4 receptors". Peptides. 27 (6): 1451–6. doi:10.1016/j.peptides.2005.10.020. PMID 16325304.
  16. ^ Catania A (July 2008). "Neuroprotective actions of melanocortins: a therapeutic opportunity". Trends in Neurosciences. 31 (7): 353–60. doi:10.1016/j.tins.2008.04.002. PMID 18550183.
  17. ^ Lasaga M, Debeljuk L, Durand D, Scimonelli TN, Caruso C (October 2008). "Role of alpha-melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation". Peptides. 29 (10): 1825–35. doi:10.1016/j.peptides.2008.06.009. hdl:11336/104816. PMID 18625277.
  18. ^ Gonzalez PV, Schiöth HB, Lasaga M, Scimonelli TN (March 2009). "Memory impairment induced by IL-1beta is reversed by alpha-MSH through central melanocortin-4 receptors". Brain, Behavior, and Immunity. 23 (6): 817–22. doi:10.1016/j.bbi.2009.03.001. hdl:11336/104814. PMID 19275930.
  19. ^ Chaki S, Oshida Y, Ogawa S, Funakoshi T, Shimazaki T, Okubo T, Nakazato A, Okuyama S (December 2005). "MCL0042: a nonpeptidic MC4 receptor antagonist and serotonin reuptake inhibitor with anxiolytic- and antidepressant-like activity". Pharmacology Biochemistry and Behavior. 82 (4): 621–6. doi:10.1016/j.pbb.2005.11.001. PMID 16337261.
  20. ^ Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S (February 2003). "Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor". The Journal of Pharmacology and Experimental Therapeutics. 304 (2): 818–26. doi:10.1124/jpet.102.044826. PMID 12538838.

External links edit

  • "Melanocortin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
  • Melanocortin+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
  • Calculated spatial position of melanocortin-4 receptor in the lipid bilayer, inactive state with antagonist and active state with agonist

April 10, 2024
melanocortin, receptor, members, rhodopsin, family, transmembrane, protein, coupled, receptors, there, five, known, members, melanocortin, receptor, system, each, with, differing, specificities, melanocortins, mc1r, mc1r, associated, with, pigmentation, geneti. Melanocortin receptors are members of the rhodopsin family of 7 transmembrane G protein coupled receptors There are five known members of the melanocortin receptor system 1 each with differing specificities for melanocortins 2 3 4 MC1R MC1R is associated with pigmentation genetics MC2R MC2R is also known as the ACTH receptor or corticotropin receptor because it is specific for ACTH alone MC3R MC3R is associated with childhood growth accrual of lean mass and onset of puberty 5 MC4R Defects in MC4R are a cause of autosomal dominant obesity accounting for 6 of all cases of early onset obesity 6 MC5R MC5RThese receptors are inhibited by endogenous inverse agonists agouti signalling peptide and agouti related peptide 7 and activated by synthetic i e afamelanotide and endogenous agonist melanocyte stimulating hormones 8 Contents 1 Selective ligands 1 1 Agonists 1 2 Antagonists and inverse agonists 1 3 Unknown 2 References 3 External linksSelective ligands editSeveral selective ligands for the melanocortin receptors are known 9 10 11 12 and some synthetic compounds have been investigated as potential tanning anti obesity and aphrodisiac drugs with tanning effects mainly from stimulation of MC1 13 while anorectic and aphrodisiac effects appear to involve both MC3 and MC4 14 MC1 MC3 and MC4 are widely expressed in the brain and are also thought to be responsible for effects on mood and cognition 15 16 17 18 Agonists edit Non selectivea MSH b MSH g MSH Afamelanotide Bremelanotide Melanotan II Modimelanotide SetmelanotideMC1 selectiveBMS 470 539MC4 selectivePF 00446687 PL 6983 THIQUnknown but for certain MC2 acting Alsactide TetracosactideAntagonists and inverse agonists edit Non selectiveAgouti related peptide Agouti signalling peptideMC4 selectiveHS 014 HS 024 MCL 0042 19 MCL 0129 20 MPB 10 SHU 9119 agonist at MC1 and MC5 antagonist at MC3 and MC4 Unknown edit SemaxReferences edit Melanocortins and the Melanocortin Receptor Archived from the original on 2007 04 11 Retrieved 2007 03 14 Voisey J Carroll L van Daal A October 2003 Melanocortins and their receptors and antagonists Current Drug Targets 4 7 586 97 doi 10 2174 1389450033490858 PMID 14535656 Hadley ME Dorr RT April 2006 Melanocortin peptide therapeutics historical milestones clinical studies and commercialization Peptides 27 4 921 30 doi 10 1016 j peptides 2005 01 029 PMID 16412534 Dores RM April 2009 Adrenocorticotropic hormone melanocyte stimulating hormone and the melanocortin receptors revisiting the work of Robert Schwyzer a thirty year retrospective Annals of the New York Academy of Sciences 1163 1 93 100 doi 10 1111 j 1749 6632 2009 04434 x PMID 19456331 Lam B Y H Williamson A Finer S et al MC3R links nutritional state to childhood growth and the timing of puberty Nature 2021 doi 10 1038 s41586 021 04088 9 Farooqi IS Keogh JM Yeo GS Lank EJ Cheetham T O Rahilly S 2003 Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene N Engl J Med 348 12 1085 95 doi 10 1056 NEJMoa022050 PMID 12646665 Chai B Pogozheva I Lai Y Li J Neubig R Mosberg H Gantz I 2005 Receptor antagonist interactions in the complexes of agouti and agouti related protein with human melanocortin 1 and 4 receptors Biochemistry 44 9 3418 31 doi 10 1021 bi0478704 PMID 15736952 Pogozheva I Chai B Lomize A Fong T Weinberg D Nargund R Mulholland M Gantz I Mosberg H 2005 Interactions of human melanocortin 4 receptor with nonpeptide and peptide agonists Biochemistry 44 34 11329 41 doi 10 1021 bi0501840 PMC 2532597 PMID 16114870 Balse Srinivasan P Grieco P Cai M Trivedi D Hruby VJ November 2003 Structure activity relationships of gamma MSH analogues at the human melanocortin MC3 MC4 and MC5 receptors Discovery of highly selective hMC3R hMC4R and hMC5R analogues Journal of Medicinal Chemistry 46 23 4965 73 doi 10 1021 jm030119t PMID 14584947 Wilson KR Todorovic A Proneth B Haskell Luevano C 2006 Overview of endogenous and synthetic melanocortin peptides Cellular and Molecular Biology Noisy le Grand France 52 2 3 20 PMID 16914082 Hruby VJ Cai M Cain JP Mayorov AV Dedek MM Trivedi D 2007 Design synthesis and biological evaluation of ligands selective for the melanocortin 3 receptor Current Topics in Medicinal Chemistry 7 11 1107 19 doi 10 2174 156802607780906645 PMC 2274922 PMID 17584128 Mayorov AV Cai M Palmer ES Dedek MM Cain JP Van Scoy AR Tan B Vagner J Trivedi D Hruby VJ January 2008 Structure activity relationships of cyclic lactam analogues of alpha melanocyte stimulating hormone alpha MSH targeting the human melanocortin 3 receptor Journal of Medicinal Chemistry 51 2 187 95 doi 10 1021 jm070461w PMC 2587288 PMID 18088090 Kadekaro AL Kanto H Kavanagh R Abdel Malek ZA June 2003 Significance of the melanocortin 1 receptor in regulating human melanocyte pigmentation proliferation and survival Annals of the New York Academy of Sciences 994 1 359 65 doi 10 1111 j 1749 6632 2003 tb03200 x PMID 12851336 King SH Mayorov AV Balse Srinivasan P Hruby VJ Vanderah TW Wessells H 2007 Melanocortin receptors melanotropic peptides and penile erection Current Topics in Medicinal Chemistry 7 11 1098 1106 doi 10 2174 1568026610707011111 PMC 2694735 PMID 17584130 Cragnolini AB Schioth HB Scimonelli TN June 2006 Anxiety like behavior induced by IL 1beta is modulated by alpha MSH through central melanocortin 4 receptors Peptides 27 6 1451 6 doi 10 1016 j peptides 2005 10 020 PMID 16325304 Catania A July 2008 Neuroprotective actions of melanocortins a therapeutic opportunity Trends in Neurosciences 31 7 353 60 doi 10 1016 j tins 2008 04 002 PMID 18550183 Lasaga M Debeljuk L Durand D Scimonelli TN Caruso C October 2008 Role of alpha melanocyte stimulating hormone and melanocortin 4 receptor in brain inflammation Peptides 29 10 1825 35 doi 10 1016 j peptides 2008 06 009 hdl 11336 104816 PMID 18625277 Gonzalez PV Schioth HB Lasaga M Scimonelli TN March 2009 Memory impairment induced by IL 1beta is reversed by alpha MSH through central melanocortin 4 receptors Brain Behavior and Immunity 23 6 817 22 doi 10 1016 j bbi 2009 03 001 hdl 11336 104814 PMID 19275930 Chaki S Oshida Y Ogawa S Funakoshi T Shimazaki T Okubo T Nakazato A Okuyama S December 2005 MCL0042 a nonpeptidic MC4 receptor antagonist and serotonin reuptake inhibitor with anxiolytic and antidepressant like activity Pharmacology Biochemistry and Behavior 82 4 621 6 doi 10 1016 j pbb 2005 11 001 PMID 16337261 Chaki S Hirota S Funakoshi T Suzuki Y Suetake S Okubo T Ishii T Nakazato A Okuyama S February 2003 Anxiolytic like and antidepressant like activities of MCL0129 1 S 2 4 fluorophenyl 2 4 isopropylpiperadin 1 yl ethyl 4 4 2 methoxynaphthalen 1 yl butyl piperazine a novel and potent nonpeptide antagonist of the melanocortin 4 receptor The Journal of Pharmacology and Experimental Therapeutics 304 2 818 26 doi 10 1124 jpet 102 044826 PMID 12538838 External links edit Melanocortin Receptors IUPHAR Database of Receptors and Ion Channels International Union of Basic and Clinical Pharmacology Melanocortin Receptors at the U S National Library of Medicine Medical Subject Headings MeSH Calculated spatial position of melanocortin 4 receptor in the lipid bilayer inactive state with antagonist and active state with agonist Retrieved from https en wikipedia org w index php title Melanocortin receptor amp oldid 1184163075, wikipedia, wiki, book, books, library,

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