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越来越多的研究表明,精氨酸加压素(arginine vasopressin,AVP)在痛觉调制中具有镇痛作用。已报道的研究专注于AVP镇痛的中枢作用机制,而本研究旨在研究AVP镇痛的的外周作用机制。应用全细胞膜片钳技术,在急性分离的大鼠背根神经节(DRG)神经元上,观察AVP对GABA激活电流(IGABA)的增强作用以及AVP对GABAA受体功能的影响。结果显示,AVP(1×10-10~1×10-5 mol/L)预处理后,IGABA增大,GABA剂量效应曲线上移,IGABA的最大值较之对照增加约49.1%;而EC50值几乎不变,表示此种加强为非竞争性的,而且AVP对GABA电流的作用可能是电压非依赖性的。AVP对IGABA的加强作用几乎完全被V1a受体的拮抗剂SR49059(3×10-6 mol/L)阻断。二次钳压技术胞内透析非水解GDP类似物GDP-β-S(5×10-4 mol/L)或PKC抑制剂GF109203X(2×10-6 mol/L)也可以阻断AVP对IGABA的加强作用。以上结果提示,AVP经由G蛋白耦联受体以及PKC信号通路上调DRG神经元GABAA受体的功能,可能是其诱导镇痛作用的基础。
More and more studies have shown that arginine vasopressin (AVP) has analgesic effect in the modulation of pain. Reported studies have focused on the central mechanism of AVP analgesia, whereas the present study aimed to study the mechanism of peripheral effects of AVP analgesia. Whole-cell patch clamp technique was used to observe the potentiation of GABA activation current (IGABA) by AVP and the effect of AVP on GABAA receptor function in acutely isolated rat DRG neurons. The results showed that the IGABA increased and the dose-response curve of GABA was up-shifted after AVP (1 × 10-10 ~ 1 × 10-5 mol / L) pretreatment, the maximum value of IGABA increased by 49.1% compared with the control; Almost unchanged, indicating that such enhancement is noncompetitive, and the effect of AVP on GABA currents may be voltage-independent. The potentiation of IGABA by AVP is almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10-6 mol / L). Secondary clamp technique Intracellular dialysis non-hydrolysed GDP analogue GDP-β-S (5 × 10-4 mol / L) or PKC inhibitor GF109203X (2 × 10-6 mol / L) can also block the effect of AVP on IGABA Strengthen the role. The above results suggest that AVP may up-regulate the GABAA receptor function of DRG neurons via G protein-coupled receptors and PKC signaling pathways, which may be the basis of its analgesic effect.