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精氨酸加压素对大鼠背根神经节神经元GABA激活电流的增强作用

邱芳, 胡旺平, 杨之帆

生物资源绿色转化湖北省协同创新中心，湖北大学生命科学学院，武汉 430062；湖北科技学院药学院，咸宁 437100

摘要

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。

关键词： 精氨酸加压素; GABA激活电流; 背根神经节; 膜片钳技术; 胞内透析

分类号：R329

Enhancement of GABA-activated currents by arginine vasopressin in rat dorsal root ganglion neurons

QIU Fang, HU Wang-Ping, YANG Zhi-Fan

Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan 430062, China； Department of Pharmacology, Hubei University of Science and Technology, Xianning 437100, China

Abstract

A growing number of studies have shown that arginine vasopressin (AVP) plays an analgesia role in the modulation of nociception. Previous studies have focused on the central mechanisms of AVP analgesia. The aim of the present study was to find out whether peripheral mechanisms are also involved. The effect of AVP on GABA-activated currents (IGABA) and GABAA receptor function in freshly isolated dorsal root ganglion (DRG) neurons of rats were studied using whole cell patch clamp technique. The result showed that, IGABA were potentiated by pre-treatment with AVP (1 × 10−10–1 × 10−5 mol/L) in a concentration-dependent manner. Meanwhile, the GABA concentration-response curve was shifted upwards, with an increase of (49.1 ± 4.0)% in the maximal current response but with no significant change in the EC50 values. These results indicate that the enhancing effect is non-competitive. In addition, the effects of AVP on IGABA might be voltage-independent. This potentiation of IGABA induced by AVP was almost completely blocked by the V1a receptor antagonist SR49059 (3 × 10−6 mol/L). Also it could be removed by intracellular dialysis of either GDP-β-S (5 × 10−4 mol/L), a non-hydrolyzable GDP analog, or GF109203X (2 × 10−6 mol/L), a selective protein kinase C (PKC) inhibitor, with the re-patch clamp. These results suggest that AVP up-regulates the function of the GABAA receptor via G protein-coupled receptors and PKC-dependent signal pathways in rat DRG neurons, and this potentiation may underlie the analgesia induced by AVP.

Key words: Arginine vasopressin; GABA-activated current; dorsal root ganglion neurons; patch clamp technique; intracellular dialysis

收稿日期：2014-03-24　　录用日期：2014-08-22

通讯作者：杨之帆　　E-mail: sailyangzhf@gmail.com

引用本文：

邱芳, 胡旺平, 杨之帆. 精氨酸加压素对大鼠背根神经节神经元GABA激活电流的增强作用[J]. 生理学报 2014; 66 (6): 647-657.

QIU Fang, HU Wang-Ping, YANG Zhi-Fan. Enhancement of GABA-activated currents by arginine vasopressin in rat dorsal root ganglion neurons. Acta Physiol Sin 2014; 66 (6): 647-657 (in Chinese with English abstract).