Melanokortinski receptor

Melanokortinski receptori su članovi porodice rodopsina od sedam transmembranskih G-protein spregnutih receptora.

Poznato je pet članova sistema receptora za melanokortin^[1] svaki sa različitim specifičnostima za melanokortine:^[2]^[3]^[4]

MC1R povezan je s pigmentacijskom genetikom;
MC2R poznat je i kao ACTH-receptor ili kortikotropinski receptor, jer je specifičan samo za ACTH;
MC3R;
MC4R: Defekti u MC4R uzrokuju autosomno dominantne gojaznosti, čineći 6% svih slučajeva gojaznosti s ranim;^[5]
MC5R.

Ovi receptori su inhibirani pomoću endogenin inverznih antagonista agouti signalmog peptida i agouti-srodnog peptida,^[6] i aktivira se sintetska (tj. afamelanotid) i endogeni agonist melanocit-stumulirajućih hormona.^[7]

Selektivni ligandi uredi

Poznato je nekoliko selektivnih liganada za receptore melanokortina ,^[8]^[9]^[10]^[11] a neki sintetski spojevi su istraženi kao potencijalni lijekovi za sunčanje, protiv gojaznosti i afrodizijaci, sa efektima štavljenja uglavnom putem stimulacije MC₁,^[12] dok se čini da anoreksijski i afrodizijski efekti uključuju i MC₃ i MC₄.^[13] MC₁, MC₃ i MC₄ su široko izraženi u mozgu, a smatra se da su odgovorni za efekte na raspoloženje i kogniciju.^[14]^[15]^[16]^[17]

Agonisti uredi

Neselektivni

MC₁-selektivni

BMS-470,539

MC₄-selektivno

Nepoznato (ali za određene MC₂-djelujući)

Antagonisti i inverzni agonisti uredi

Neselektivni

MC₄-selektivni

HS-014
HS-024
MCL-0042^[18]
MCL-0129^[19]
MPB-10
SHU-9119 (agonist MC₁ i MC₅, antagonist MC₃ i MC₄)

Nepoznati uredi

Semaks

Reference uredi

^ "Melanocortins and the Melanocortin Receptor". Arhivirano s originala, 11. 4. 2007. Pristupljeno 14. 3. 2007.
^ Voisey J, Carroll L, van Daal A (oktobar 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.
^ 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 (novembar 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 (januar 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 (juni 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, Schiöth HB, Scimonelli TN (juni 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 (juli 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 (oktobar 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 (mart 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 (decembar 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 (februar 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.

Vanjski linkovi uredi

"Melanocortin Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano s originala, 30. 1. 2021. Pristupljeno 17. 1. 2021.
Melanocortin Receptors na US 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

Šablon:G-protein spregniti receptori Šablon:Modulatori receptora melanokortina

[1] "Melanocortins and the Melanocortin Receptor". Arhivirano s originala, 11. 4. 2007. Pristupljeno 14. 3. 2007.

[pmid14535656-2] Voisey J, Carroll L, van Daal A (oktobar 2003). "Melanocortins and their receptors and antagonists". Current Drug Targets. 4 (7): 586–97. doi:10.2174/1389450033490858. PMID 14535656.

[pmid16412534-3] 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.

[pmid19456331-4] 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] 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.

[6] 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.

[7] 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.

[pmid14584947-8] Balse-Srinivasan P, Grieco P, Cai M, Trivedi D, Hruby VJ (novembar 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.

[pmid16914082-9] 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.

[pmid17584128-10] 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.

[pmid18088090-11] Mayorov AV, Cai M, Palmer ES, Dedek MM, Cain JP, Van Scoy AR, Tan B, Vagner J, Trivedi D, Hruby VJ (januar 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.

[pmid12851336-12] Kadekaro AL, Kanto H, Kavanagh R, Abdel-Malek ZA (juni 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.

[pmid17584130-13] 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.

[pmid16325304-14] Cragnolini AB, Schiöth HB, Scimonelli TN (juni 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.

[pmid18550183-15] Catania A (juli 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.

[pmid18625277-16] Lasaga M, Debeljuk L, Durand D, Scimonelli TN, Caruso C (oktobar 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.

[pmid19275930-17] Gonzalez PV, Schiöth HB, Lasaga M, Scimonelli TN (mart 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.

[pmid16337261-18] Chaki S, Oshida Y, Ogawa S, Funakoshi T, Shimazaki T, Okubo T, Nakazato A, Okuyama S (decembar 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.

[pmid12538838-19] Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S (februar 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.

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