Melanokortinski receptor
Melanokortin receptori su članovi rodopsin familije 7-transmembranskih G protein-spregnutih receptora.
Pet članova melanokortin receptorskog sistema je poznato[1] svaki od kojih ima osobenu specifičnost za melanokortine,[2][3][4]
- MC1R. MC1R je asociran sa genetikom pigmentacije.
- MC2R. MC2R je takođe poznat kao ACTH receptor ili kortikotropin receptor.
- MC3R. MC3R
- MC4R. MC4R defekti su uzrok autozomalno dominantne gojaznosti, koja sačinjava 6% svih slučajeva rane gojaznosti.[5]
- MC5R. MC5R
Ovi receptori su inhibirani endogenim inverznim agonistima agouti signalni peptid i agutiju srodni peptid,[6] i aktivirani sintetičkim (ie: afamelanotid) i endogenim agonistima melanocit-stimulišući hormonima.[7]
Selektivni Ligandi
Više selektivnih liganda melanokortin receptora je poznato,[8][9][10][11] i neka sintetička jedinjenja su bila istražena kao potencijalna sredstva za dobijanje tena, i kao lekovi protiv gojaznosti. Potamnjivanje kože je prvenstveno uzrokovano MC1 stimulacijom,[12] dok su anoreksični efekti posredovani MC3 i MC4 receptorima.[13] MC1, MC3 i MC4 su široko izraženi u mozgu, i smatra se da su odgovorni za razne efekte raspoloženja i spoznaje.[14][15][16][17]
2
Literatura
- ↑ „Melanocortins and the Melanocortin Receptor”. Arhivirano iz originala na datum 2007-04-11. Pristupljeno 2014-04-21.
- ↑ 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: 93–100. DOI:10.1111/j.1749-6632.2009.04434.x. PMID 19456331.
- ↑ 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”. The New England Journal of Medicine 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: 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. PMC 2694735. PMID 17584130.
- ↑ 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.
- ↑ 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. PMID 18625277.
- ↑ 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. 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.
- p
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Drugi | Moždano specifični angiogenezni inhibitor (1, 2, 3) • Cadherin (1, 2, 3) • Kalcitonin • CALCRL • CD97 • Kortikotropin-oslobađajući hormon (1, 2) • EMR (1, 2, 3) • Glukagon (GR, GIPR, GLP1R, GLP2R) • Hormon rasta oslobađajući hormon • PACAPR1 • GPR • Latrofilin (1, 2, 3, ELTD1) • Metuselah-slični proteini • Paratiroidni hormon (1, 2) • Sekretin • Vazoaktivni intestinalni peptid (1, 2) |
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glutamat / feromon
Drugi |
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Frizzled / Zaglađeni
Uvojiti | |
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Zaglađeni |
B trdu: peptidi (nrpl/grfl/cytl/horl), receptori (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd, signalni putevi (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)
