Purinergic Receptors in the Balance

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scalesP2X7 receptors are cation-permeable, ATP-gated ion channels found on cells of immunological origin, including peripheral macrophages and glial cells in the CNS. Studies in P2X7 receptor knockout mice have suggested a specific role in inflammatory and neuropathic pain states, and there has been considerable interest in developing P2X7 receptor-selective antagonists for the treatment of inflammatory conditions and pain.

A report in the Oct 22 early edition of PNAS, however, suggests that direct blocking of P2X7 receptors may not be the best strategy for reducing pain or lessening neuronal degeneration. The report shows that P2X7 receptors in satellite cells play a crucial role in maintaining proper P2X3 receptor expression in dorsal root ganglia. Reducing P2X7 receptor expression using siRNA, or blocking P2X7 receptor activity by antagonists, was found to cause up-regulation of P2X3 receptors, leading to increased activity of sensory neurons responding to painful stimuli and evoking abnormal nociceptive behaviours in rats.


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