Muskarinski acetilholinski receptor M5
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
[уреди | уреди извор]Visoko selektivni agonisti ili antagonisti za M5 receptor nisu pozanati (2009). Nekoliko neselektivnih muskarinskih agonista i antagonista ima znatan afinitet za M5.
Agonisti
[уреди | уреди извор]- Milamelin (E)-1,2,5,6-Tetrahidro-1-metil-3-piridinkarboksaldehid-O-metiloksim
- Sabkomelin
Pozitivni alosterni modulatori
[уреди | уреди извор]- VU-0238429: EC50 = 1.16 μM; >30 puta selektivniji u odnosu na M1 i M3, neaktivan na M2 i M4.[1]
Antagonisti
[уреди | уреди извор]Reference
[уреди | уреди извор]- ^ Bridges TM; Marlo JE; Niswender CM; et al. (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. PMID 19438238. doi:10.1021/jm900286j.
- ^ Grant MK, El-Fakahany EE (2005). „Persistent binding and functional antagonism by xanomeline at the muscarinic M5 receptor”. J. Pharmacol. Exp. Ther. 315 (1): 313—9. PMID 16002459. doi:10.1124/jpet.105.090134.
Literatura
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