Pharmacology of P2X channels

被引:253
作者
Gever, Joel R.
Cockayne, Debra A.
Dillon, Michael P.
Burnstock, Geoffrey
Ford, Anthony P. D. W.
机构
[1] Roche Palo Alto, Dept Biochem Pharmacol, Palo Alto, CA 94304 USA
[2] Roche Palo Alto, Dept Neurosci, Palo Alto, CA 94304 USA
[3] Roche Palo Alto, Dept Med Chem, Palo Alto, CA 94304 USA
[4] UCL Royal Free & Univ Coll Med Sch, Autonom & Neurosci Ctr, London NW3 2PF, England
来源
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY | 2006年 / 452卷 / 05期
关键词
P2X; purinergic; ATP; ion channel; antagonist;
D O I
10.1007/s00424-006-0070-9
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Significant progress in understanding the pharmacological characteristics and physiological importance of homomeric and heteromeric P2X channels has been achieved in recent years. P2X channels, gated by ATP and most likely trimerically assembled from seven known P2X subunits, are present in a broad distribution of tissues and are thought to play an important role in a variety of physiological functions, including peripheral and central neuronal transmission, smooth muscle contraction, and inflammation. The known homomeric and heteromeric P2X channels can be distinguished from each other on the basis of pharmacological differences when expressed recombinantly in cell lines, but whether this pharmacological classification holds true in native cells and in vivo is less well-established. Nevertheless, several potent and selective P2X antagonists have been discovered in recent years and shown to be efficacious in various animal models including those for visceral organ function, chronic inflammatory and neuropathic pain, and inflammation. The recent advancement of drug candidates targeting P2X channels into human trials, confirms the medicinal exploitability of this novel target family and provides hope that safe and effective medicines for the treatment of disorders involving P2X channels may be identified in the near future.
引用
收藏
页码:513 / 537
页数:25
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