Muskarinski acetilholinski receptor M₅

Muskarinski acetilholinski receptor M5
Identifikatori
Simboli	CHRM5; HM5; MGC41838
Vanjski ID	OMIM: 118496 MGI: 109248 HomoloGene: 22697 IUPHAR: M5 GeneCards: CHRM5 Gene
Ontologija gena
Molekularna funkcija	• aktivnost fosfatidilinozitol fosfolipaze C; • receptorska aktivnost; • aktivnost G protein spregnutog receptora; • aktivnost muskarinskog acetilholinskog receptora;
Celularna komponenta	• ćelijska membrana; • integralno sa ćelijskom membranom; • ćelijski spoj; • sinapsa; • postsinaptička membrana;
Biološki proces	• inhibicija aktivnosti adenilat ciklaze muskarinskim acetilholinskim receptorima; • signalni put muskarinskog acetilholinskog receptora; • ćelijska proliferacija; • dopaminski transport; • transmisija nervnog impulsa; • regulacija fosfatidilinozitolne defosforilacije;
Pregled RNK izražavanja
	podaci
Ortolozi

edit

Ljudski muskarinski acetilholinski receptor M₅, kodiran CHRM5 genom, je član superfamilije integralnih membranskih proteina G protein spregnutih receptora. Vezivanje endogenog liganda acetilholina za M₅ receptor postiče brojne ćelijske odgovore kao što je inhibicija adenilat ciklaze, degradacija fosfoinozitida, i modulacija kalijumskog kanala. Muskarinski receptori posreduju mnoge efekte acetilholina u centralnom i perifernom nervnom sistemu. Kliničke implikacije ovog receptora nisu potpuno istražene. Poznato je da stimulacija ovog receptora efektivno snižava nivoe cikličnog AMP-a i umanjuje aktivnost proteinske kinaze A (PKA).

Ligandi

Visoko selektivni agonisti ili antagonisti za M₅ receptor nisu pozanati (2009). Nekoliko neselektivnih muskarinskih agonista i antagonista ima znatan afinitet za M₅.

Agonisti

Milamelin (E)-1,2,5,6-Tetrahidro-1-metil-3-piridinkarboksaldehid-O-metiloksim
Sabkomelin

Pozitivni alosterni modulatori

VU-0238429: EC₅₀ = 1.16 μM; >30 puta selektivniji u odnosu na M1 i M3, neaktivan na M2 i M4.^[1]

Antagonisti

Ksanomelin^[2]

Reference

↑ Bridges TM, Marlo JE, Niswender CM, et al. (June 2009). „Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins”. J. Med. Chem. 52 (11): 3445–8. DOI:10.1021/jm900286j. PMID 19438238.
↑ Grant MK, El-Fakahany EE (October 2005). „Persistent binding and functional antagonism by xanomeline at the muscarinic M₅ receptor”. J. Pharmacol. Exp. Ther. 315 (1): 313–9. DOI:10.1124/jpet.105.090134. PMID 16002459.

Literatura

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Kohn EC, Alessandro R, Probst J, et al. (1996). „Identification and molecular characterization of a m5 muscarinic receptor in A2058 human melanoma cells. Coupling to inhibition of adenylyl cyclase and stimulation of phospholipase A2.”. J. Biol. Chem. 271 (29): 17476–84. DOI:10.1074/jbc.271.29.17476. PMID 8663391.
Burstein ES, Spalding TA, Brann MR (1998). „The second intracellular loop of the m5 muscarinic receptor is the switch which enables G-protein coupling.”. J. Biol. Chem. 273 (38): 24322–7. DOI:10.1074/jbc.273.38.24322. PMID 9733718.
Sato KZ, Fujii T, Watanabe Y, et al. (1999). „Diversity of mRNA expression for muscarinic acetylcholine receptor subtypes and neuronal nicotinic acetylcholine receptor subunits in human mononuclear leukocytes and leukemic cell lines.”. Neurosci. Lett. 266 (1): 17–20. DOI:10.1016/S0304-3940(99)00259-1. PMID 10336173.
Wang H, Han H, Zhang L, et al. (2001). „Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart.”. Mol. Pharmacol. 59 (5): 1029–36. PMID 11306684.
Buchli R, Ndoye A, Arredondo J, et al. (2002). „Identification and characterization of muscarinic acetylcholine receptor subtypes expressed in human skin melanocytes.”. Mol. Cell. Biochem. 228 (1–2): 57–72. DOI:10.1023/A:1013368509855. PMID 11855742.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). „Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. DOI:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Fujii T, Watanabe Y, Inoue T, Kawashima K (2003). „Upregulation of mRNA encoding the M5 muscarinic acetylcholine receptor in human T- and B-lymphocytes during immunological responses”. Neurochem. Res. 28 (3–4): 423–9. DOI:10.1023/A:1022840416292. PMID 12675126.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). „Complete sequencing and characterization of 21,243 full-length human cDNAs”. Nat. Genet. 36 (1): 40–5. DOI:10.1038/ng1285. PMID 14702039.
De Luca V, Wang H, Squassina A, et al. (2004). „Linkage of M5 muscarinic and alpha7-nicotinic receptor genes on 15q13 to schizophrenia”. Neuropsychobiology 50 (2): 124–7. DOI:10.1159/000079102. PMID 15292665.
Qu J, Zhou X, Xie R, et al. (2006). „The presence of m1 to m5 receptors in human sclera: evidence of the sclera as a potential site of action for muscarinic receptor antagonists”. Curr. Eye Res. 31 (7–8): 587–97. DOI:10.1080/02713680600770609. PMID 16877267.
Anney RJ, Lotfi-Miri M, Olsson CA, et al. (2007). „Variation in the gene coding for the M5 muscarinic receptor (CHRM5) influences cigarette dose but is not associated with dependence to drugs of addiction: evidence from a prospective population based cohort study of young adults”. BMC Genet. 8: 46. DOI:10.1186/1471-2156-8-46. PMC 1978498. PMID 17608938.

Povezano

Muskarinski acetilholinski receptor

[pmid19438238-1] Bridges TM, Marlo JE, Niswender CM, et al. (June 2009). „Discovery of the first highly M5-preferring muscarinic acetylcholine receptor ligand, an M5 positive allosteric modulator derived from a series of 5-trifluoromethoxy N-benzyl isatins”. J. Med. Chem. 52 (11): 3445–8. DOI:10.1021/jm900286j. PMID 19438238.

[pmid16002459-2] Grant MK, El-Fakahany EE (October 2005). „Persistent binding and functional antagonism by xanomeline at the muscarinic M₅ receptor”. J. Pharmacol. Exp. Ther. 315 (1): 313–9. DOI:10.1124/jpet.105.090134. PMID 16002459.

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