Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons

被引:170
作者
Ueno, S
Tsuda, M
Iwanaga, T
Inoue, K
机构
[1] Natl Inst Hlth Sci, Div Pharmacol, Setagaya Ku, Tokyo 158, Japan
[2] Hokkaido Univ, Grad Sch Vet Med, Dept Biomed Sci, Sapporo, Hokkaido 060, Japan
关键词
dorsal root ganglia; P2X; ATP; capsaicin; patch-clamp; in situ hybridization; pain;
D O I
10.1038/sj.bjp.0702319
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of male adult rat (Wistar) dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DRG neurons from adult rats type using capsaicin sensitivity. 2 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 relationship between current kinetics and capsaicin-sensitivity. 3 Both types of neurons were responsive to ATP and alpha, beta methylene-ATP (alpha,beta meATP). The concentration of alpha,beta meATP producing half-maximal activation (EC50) Of neurons with fast desensitization was less (11 mu M) than that of neurons with slow desensitization (63 mu M), while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid tetrasodium (PPADS) antagonized alpha,beta meATP-induced currents in both types of neurons. 4 In situ hybridization revealed that small cells of the DRG predominantly expressed mRNAs of P2X(3) and medium-sized cells expressed mRNAs of P2X(2) and P2X(3). In contrast, both of mRNAs were not detected in large cells of the DRG. 5 These results suggest that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X(3) subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X(2) and P2X(3).
引用
收藏
页码:429 / 436
页数:8
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