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One-way cross-desensitization between P2X purinoceptors and vanilloid receptors in adult rat dorsal root ganglion neurones

A. S. Piper and R. J. Docherty

1. Capsaicin and ATP can activate ligand-gated cation channels in nociceptive rat dorsal root ganglion (DRG) neurones. We have studied cross-desensitization between these two agents in rat isolated DRG neurones using the whole-cell voltage-clamp technique.

2. ATP (10 µM) activated an inward current in DRG neurones at a holding potential of -60 mV. ATP evoked 'fast' responses that underwent rapid activation and desensitization, 'slow' responses that activated and desensitized more slowly, or responses that displayed a mixture of these two characteristics. The time course of the response to ATP was not related obviously to capsaicin sensitivity.

3. Prior application of capsaicin (0·5 µM) increased the proportion of cells displaying only fast responses to ATP (10 µM) suggesting that cross-desensitization had occurred between capsaicin and the slow component of the ATP response. Prior desensitization to ATP had no apparent effect on the inward current response to capsaicin (0·5 µM).

4. Cross-desensitization between capsaicin and ATP was Ca²⁺ dependent.

5. Changing the membrane holding potential (V_h) to +40 mV for a brief period before applying ATP at -60 mV had a similar effect to capsaicin, i.e. the proportion of cells displaying only fast responses to ATP was increased significantly. This effect of depolarization was not Ca²⁺ dependent.

6. The heterogenity of responses to ATP is probably due to co-expression of homomeric P2X₃ receptors and heteromeric receptors comprising P2X₃ subunits with other P2X subunits. We propose that the change in time course of the ATP response produced by prior desensitization to capsaicin is due to selective cross-desensitization with the heteromeric P2X receptors.

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