A neuropharmacological Research for the Function of ATP Receptors in the Nociception

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The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of rat dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DFG neurons from adult rats type using capsaicin sensitivity. Two types of ATP-activated currents, one with fast, the other with slow desensitization, were found under voltage-clamp conditions. In addition, cells with fast but not slow desensitization responded to capsaicin, indicating that there was a mutual relevance between current kinetics and capsaicin-sensitivity. Both types of neurons were responsive to ATP and α,β-methylene-ATP (α,βmeATP). The concentration of α,βmeATP producing half-maximal activation (EC50) of neurons with fast desensitization was less (11 μM) than that of neurons with slow desensitization (63 μM) , while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS) antagonized α,βmeATP-induced currents in both types of neurons. At the RNA level, small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed FNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large cells of the DRG. These results suggested that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3.