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Fast‐desensitizing P2X₃ receptors of nociceptive dorsol root ganglion (DRG) neurons are thought to mediate pain sensation. Since P2X₃ receptor efficiency is powerfully modulated by desensitization, its underlying properties were studied with patch‐clamp recording.

On rat cultured DRG neurons, 2 s application of ATP (EC₅₀=1.52 μM), ADP (EC₅₀=1.1 μM) or α,β‐meATP (EC₅₀=1.78 μM) produced similar inward currents that fully desensitized, at the same rate, back to baseline. Recovery from desensitization was much slower after ATP and ADP than after α,β‐meATP and, in all cases, it had sigmoidal time course.

By alternating the application of ATP and α,β‐meATP, we observed complete cross‐desensitization indicating that these agonists activated the same receptors. This notion was confirmed by the similar antagonism induced by 2′, 3′‐O‐(2,4,6,trinitrophenyl)‐adenosine triphosphate (TNP‐ATP …