P物质对大鼠三叉神经节神经元GABA-和5-HT-激活电流的反向调制作用(英文)

Opposite modulatory effects of substance Pon GABA-and 5-HT-activated currents inthe same sensory neurons

实验采用全细胞膜片钳技术观察P 物质(SP)对大鼠同一三叉神经节(TG)神经元γ-氨基丁酸激活电流(IGABA)和5-羟色胺激活电流(I5-HT)的调制作用。在受检的47 个 TG 细胞中,多数情况下可在同一细胞记录到IGABA 和 I5-HT 两种电流(63.8%,30/47)。在 30 个同时对 GABA 和 5-HT 敏感的细胞,其中 22 个细胞预加 SP(0.01 μmol/L)后,IGABA 减小(35.7 ± 6.1)%,而I5-HT 增加(65.2 ±8.7)%。此种调制作用可被SP 受体拮抗剂GR82334 及胞内透析GDP-β -S 或GF109203X 所阻断。以上结果表明:SP 受体激活后经G 蛋白耦联,通过相同的PLC-DAG-PKC 转导途径对同一感觉神经元共存的GABAA 受体和5-HT3 受体产生相反的调制效应。

The modulation by substance P of γ-aminobutyric acid (GABA)- and 5-hydroxytryptamine (5-HT)-activated currents (IGABA and I5-HT) was studied by using patch-clamp technique in rat trigeminal ganglion (TG) neurons. The majority of neurons examined responded to GABA and 5-HT with inward currents in the same cells (63.8%, 30/47). In 22 out of 30 neurons sensitive to both GABA and 5-HT, pretreatment with substance P (SP, 0.01 μmol/L) suppressed IGABA by (35.7 ± 6.1)% and enhanced I5-HT by (65.2 ± 8.7)%. GR 82334, a potent and specific antagonist of NK1 tachykinin receptor, reversibly blocked the modulatory effects of SP. The SP modulation on IGABA and I5-HT was also abolished by intracellular dialysis of GDP-β-S, a non-hydrolyzable GDP analog, or GF 109203X, a selective protein kinase C inhibitor. These results suggest that SP exerts opposite modulatory actions on GABAA receptor and 5-HT3 receptor activity of the same primary sensory neuron via the same intracellular signal transduction pathway.