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Front Pharmacol. 2018 Nov 8;9:1238. doi: 10.3389/fphar.2018.01238. eCollection 2018.

Identification of Glycine Receptor α3 as a Colchicine-Binding Protein.

Author information

1
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.
2
School of Bioscience and Biotechnology, Chengdu Medical College, Chengdu, China.
3
Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Department of Gynecology and Obstetrics, West China Second University Hospital, Sichuan University, Chengdu, China.
4
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Abstract

Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyRα3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyRα3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyRα3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyRα3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations.

KEYWORDS:

colchicine; glycine receptor alpha 3; gouty arthritis; inflammatory pain; virtual target identification

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