吗啡依赖大鼠脊髓和脑干μ受体和κ受体mRNA表达的研究1

中国临床药理学与治疗学 ›› 2000, Vol. 5 ›› Issue (1): 1-5.

• 论著 • 下一篇

吗啡依赖大鼠脊髓和脑干μ受体和κ受体mRNA表达的研究¹

刘惠芬, 谢小虎, 周文华², 杨国栋

宁波戒毒研究中心;
²宁波微循环与莨菪类药研究所,宁波 315010

收稿日期:1999-10-19 修回日期:2000-01-30 出版日期:2000-03-26 发布日期:2020-11-26
作者简介:刘惠芬,女,助理研究员.主要从事分子生物学研究;杨国栋,男,研究员,从事阿片依赖的机制和防治研究。
基金资助:
1本课题由浙江省医药卫生科研项目(980A093)和国家科技部科技攻关项目(94Z05)资助

Expression ofμandκopiate receptor in spinal cord and brainstem during morphine withdrawal in rats

LIU Hui-Fen, XIE Xiao-Hu, ZHOU Wen-Hua, YANG Guo-Dong

Ningbo Addiction Research and Treatment Center,Ningbo Institute of Microcirculation and Henbane,Ningbo 315010

Received:1999-10-19 Revised:2000-01-30 Online:2000-03-26 Published:2020-11-26

摘要/Abstract

摘要： 目的观察吗啡依赖戒断时大鼠脊髓和脑干μ受体和κ受体 mRNA 表达以及毒蕈碱受体拮抗剂、 NMDA 受体拮抗剂和 NOS 抑制剂对这些基因表达的影响。方法用逆转录聚合酶链反应(RT -PCR),以β-actin mRNA 为内标检测μ受体和κ受体 mRNA 的表达水平。结果吗啡依赖大鼠脊髓和脑干μ受体 mRNA 表达明显升高,纳洛酮激发大鼠戒断反应 1h 后μ受体基因表达降低,4h 后接近正常组,而脊髓和脑干κ受体基因的变化与μ受体基因表达趋势相反。鞘内注射 PKA 抑制剂 Rp-cAMPs 和蛋白磷酸酶抑制剂 calyculin A 可以明显减少脊髓和脑干中μ受体和κ受体基因表达,而 PKA 激活剂 Sp-cAMPs 则无明显影响;经 NOS 抑制剂 l-N-硝基精氨酸甲酯(l-NAME)处理后,脊髓μ受体和κ受体基因表达明显减少,经毒蕈碱(M)受体拮抗剂甲基东莨菪碱处理后,脊髓μ受体和脑干κ受体基因表达也明显减少,而脊髓κ受体和脑干μ受体基因表达变化不明显;经 NMDA 拮抗剂 MK801和 M1受体拮抗剂哌拉唑嗪处理后,脊髓和脑干μ受体和κ受体基因表达较戒断 1h 组无明显差异。脊髓和脑干中β-actin 基因表达各处理组之间没有差别。结论吗啡依赖和戒断动物脊髓和脑干中μ受体和κ受体基因表达发生改变,M受体拮抗剂和 NOS 抑制剂在吗啡戒断反应时减少μ受体和κ受体基因表达可能是它们有效控制吗啡戒断症状的机制之一。

关键词: 吗啡, 戒断反应, μ受体, κ受体, 毒蕈碱受体, NMDA

Abstract: Aim To observe the gene expression ofμandκopiate receptor in spinal cord and brainstem,and the effects of muscarinic receptor antagonist,NMDA receptor antagonists and inhibitor of nitricoxide synthase on the expression of these genes during morphine withdrawal in rats.Methods The mRNA levels ofμandκopiate receptor mRNA were assayed by reverse transcription polymerase chain reaction (RT-PCR)with the beta-actin mRNA as an internal control.Results Theμopiate receptor mRNA levels were increased significantly in spinal cord and brainstem during morphine dependence,and decreased after injection of naloxone during morphine withdrawal in rats.Theκopiate receptor mRNA levels in spinal cord and brainstem were changed conversely compared with theμopiate receptor mRNA levels during morphine dependence and withdrawal.Theμandκopiate receptor mRNA levels in spinal cord and brainstem were decreased by administration of either Rp-cAMPs or calyculin A while these levels were not changed by Sp-cAMPs at half hour before injection of naloxone in morphine dependent rats.Administration of l-N-nitric arginine methylester(10mg·kg^-1)resulted in a decrease ofμopiate receptor andκopiate receptor levels in spinal cord,andμopiate receptor levels in spinal cord andκopiate receptor levels in brainstem were dedcreased by pretreatment with methyl-scopolamine (0.5mg·kg^-1)during morphine withdrawal.However,theμandκopiate receptor levels in both spinal cord and brainstem were not different from those of morphine withdrawal rats pretreated with either MK801 (0.125mg·kg^-1)or pirezenpine(10mg·kg^-1).In adddition,β-actin mRNA levels were not different in each group.Conclusion The expression ofμopiate receptor andκopiate receptor mRNA plays an important role in mediating the process of morphine dependence and withdrawal,and the expression ofμopiate receptor andκopiate receptor mRNA in spinal cord and brainstem could be inhibited by block of muscarinic receptor or inhibition of nitric oxide production.

Key words: morphine, withdrawal, μ opiate receptor, κ opiate receptor, muscarinic receptor, NMDA receptor

中图分类号:

R971.1

刘惠芬, 谢小虎, 周文华, 杨国栋. 吗啡依赖大鼠脊髓和脑干μ受体和κ受体mRNA表达的研究¹[J]. 中国临床药理学与治疗学, 2000, 5(1): 1-5.

LIU Hui-Fen, XIE Xiao-Hu, ZHOU Wen-Hua, YANG Guo-Dong. Expression ofμandκopiate receptor in spinal cord and brainstem during morphine withdrawal in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2000, 5(1): 1-5.

参考文献

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吗啡依赖大鼠脊髓和脑干μ受体和κ受体mRNA表达的研究¹

Expression ofμandκopiate receptor in spinal cord and brainstem during morphine withdrawal in rats

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