过刊浏览

MrgC受体激活翻转慢性应用吗啡诱发的谷氨酸转运体和nNOS改变

黄浩, 李琦, 洪炎国, 王冬梅^*

福建师范大学生命科学学院，福建省发育和神经生物学重点实验室，福州 350108

摘要

本研究旨在探讨激活MrgC受体(Mas-related gene C receptors)调制吗啡耐受的细胞学机制。对大鼠连续6天鞘内注射10 µL生理盐水、吗啡(20 µg)、吗啡+牛肾上腺髓质8-22 (bovine adrenal medulla 8-22，BAM8-22，1 nmol，隔天注射) 或 (Tyr6)-2-MSH-6-12 (MSH，5 nmol，隔天注射)；用Western blot、免疫组织化学和实时荧光定量PCR的方法检测脊髓和背根神经节(dorsal root ganglion, DRG)中与吗啡耐受相关分子的表达。结果显示：鞘内给予选择性MrgC受体激动剂BAM8-22或MSH，能抑制慢性应用吗啡所诱发的脊髓背角和/或DRG中谷氨酸转运体(GLAST、GLT-1、EAAC1)的减少和神经元型一氧化氮合酶(neuronal nitric oxide synthase, nNOS)的增加。此外，检测到MrgC受体样免疫活性表达于脊髓背角浅层；慢性应用吗啡使脊髓背角MrgC受体样免疫活性和DRG中MrgC受体 mRNA水平都增加。这些结果提示，MrgC受体通过抑制慢性应用吗啡所诱发的脊髓和DRG中的痛介质增加，而抑制吗啡耐受。

关键词： MrgC受体; 吗啡耐受; 谷氨酸转运体; 神经元型一氧化氮合酶

分类号：Q426

[MrgC receptor activation reverses chronic morphine-evoked alterations of glutamate transporters and nNOS in rats.] [Article in Chinese]

HUANG Hao, LI Qi, HONG Yan-Guo, WANG Dong-Mei^*

Provincial Key Laboratory of Developmental and Neurological Biology, College of Life Sciences, Fujian Normal University, Fuzhou 350108, China

Abstract

This study was aimed to investigate the mechanisms underlying the modulation effect of Mas-related gene (Mrg) C receptors (MrgC) on morphine tolerance. Saline, morphine (20 μg), morphine plus bovine adrenal medulla 8-22 (BAM8-22, 1 nmol) or (Tyr⁶)-2-MSH-6-12 (MSH, 5 nmol) were administered intrathecally in rats for 6 days. Pain-related molecules in the spinal cord and dorsal root ganglion (DRG) were examined using Western blot, immunocytochemistry and RT-PCR techniques. The results showed that intrathecal administration of the selective MrgC receptor agonists (BAM8-22 or MSH) remarkably attenuated or abolished chronic morphine-evoked reduction in glutamate transporters (GLAST, GLT-1 and EAAC1) in the spinal cord and increase in neuronal nitric oxide synthase (nNOS) in the spinal cord as well as DRG. In addition, MrgC receptor-like immunoreactivity (IR) was detected in superficial laminae of the spinal cord. Chronic morphine induced significant increases in MrgC receptor-IR in the spinal cord and MrgC receptor mRNA levels in DRG. These results suggest that the modulation of pro-nociceptive mediators in the spinal cord and DRG underlies the inhibition of morphine tolerance by MrgC receptor activation.

Key words: Mas-related gene (Mrg) C receptors; morphine tolerance; glutamate transporter; neuronal nitric oxide synthase

收稿日期：2013-12-04　　录用日期：2014-02-01

通讯作者：王冬梅　　E-mail: dmwang@fjnu.edu.cn

引用本文：

黄浩, 李琦, 洪炎国, 王冬梅. MrgC受体激活翻转慢性应用吗啡诱发的谷氨酸转运体和nNOS改变[J]. 生理学报 2014; 66 (4): 449-456.

HUANG Hao, LI Qi, HONG Yan-Guo, WANG Dong-Mei. [MrgC receptor activation reverses chronic morphine-evoked alterations of glutamate transporters and nNOS in rats.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (4): 449-456 (in Chinese with English abstract).