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P2X Receptors: Targets for Novel Analgesics?Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Glasgow, Scotland, UK, c.kennedy{at}strath.ac.uk The ability of adenosine 5'-triphosphate (ATP) to evoke acute pain has been known for many years, but its role in nociceptive signaling is only now becoming clear. ATP acts via P2X and P2Y receptors, and of particular importance here is the P2X3 receptor. It is expressed selectively at high levels in nociceptive sensory neurons, where it forms functional receptors on its own and in combination with the P2X2 receptor. Recent reports using gene knockout methods; antisense oligonucleotide and small, interfering RNA technologies; and a novel, selective P2X3 antagonist, A-317491, show that P2X3 receptors are involved in chronic inflammatory and neuropathic pain. The mRNA for other P2X subunits is also found in sensory neurons, and there is evidence for functional P2X1/5 or P2X2/6 heteromers in some of these. These data support the possibility that P2X receptors, particularly the P2X3 subtype, could be targeted in the search for new, effective analgesics.
Key Words: P2X receptors • P2Y receptors • Pain
The Neuroscientist, Vol. 11, No. 4,
345-356 (2005) This article has been cited by other articles:
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