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吗啡促进大鼠星形胶质细胞外ATP的酶解和腺苷的生成

刘微^*, 杨战利, 周乐全, 李小英, 闫福曼, 关莉, 刘海梅, 冯鉴强

广州中医药大学基础医学院生理学教研室，广州 510006；中山大学中山医学院生理学教研室，广州 510080

摘要

近年来的研究表明星形胶质细胞在ATP的降解和腺苷的生成方面发挥了重要的作用，而ATP和腺苷与痛觉的形成有着密切关系。本文旨在探讨镇痛药物吗啡是否能够影响星形胶质细胞酶解ATP以及生成腺苷。通过检测大鼠脑星形胶质细胞内钙的水平选择合适的吗啡孵育时间，应用高效液相色谱(high performance liquid chromatography, HPLC)检测ATP和腺苷的水平。结果显示：(1)同其他处理时间点相比，1.5和48 h的吗啡处理对ATP酶解的促进作用更为显著，而二者相比没有统计学差别。(2)对于镇痛物质腺苷，同对照组相比，1.5 h的吗啡处理能够上调腺苷生成速度，而48 h的吗啡处理后腺苷生成速度同对照组没有差异。以上结果提示，体外应用吗啡能够动态地改变星形胶质细胞外ATP和腺苷的水平，星形胶质细胞可以被认为是吗啡改变中枢神经系统ATP和腺苷水平的靶细胞之一。

关键词： 吗啡; ATP; 腺苷; 星形胶质细胞

分类号：R338

Morphine treatment enhances extracellular ATP enzymolysis and adenosine generation in rat astrocytes

LIU Wei^*, YANG Zhan-Li, ZHOU Le-Quan, LI Xiao-Ying, YAN Fu-Man, GUAN Li, LIU Hai-Mei, FENG Jian-Qiang

Department of Physiology, College of Fundamental Medical Science, Guangzhou University of Chinese Medicine, Guangzhou 510006, China； Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510080, China. E-mail: weiliu1980@yahoo.com.

Abstract

Recent studies have shown that astrocytes play important roles in ATP degradation and adenosine (a well known analgesic molecule) generation, which are closely related to pain signaling pathway. The aim of this study was to investigate whether morphine, a well known analgesic drug, could affect the speeds of ATP enzymolysis and adenosine generation in rat astrocytes. Intracellular calcium concentration ([Ca(2+)](i)) of astrocyte was measured by flow cytometry, and the time points that morphine exerted notable effects were determined for subsequent experiments. Cultured astrocytes were pre-incubated with morphine (1 μmol/L) and then were incubated with substrates, ATP and AMP, for 30 min. The speeds of ATP enzymolysis and adenosine generation were measured by high performance liquid chromatography (HPLC). The results showed that both 1.5 and 48 h of morphine pre-incubation induced maximal ATP enzymolysis speed in astrocytes among all the time points, and there was no statistical difference of ATP enzymolysis speed between morphine treatments for 1.5 and 48 h. As to adenosine, morphine pre-incubation for 1.5 h statistically increased adenosine generation, which was degraded from AMP, in cultured astrocytes compared with control group. However, no difference of adenosine generation was observed after 48 h of morphine pre-incubation. These results indicate that treatment of morphine in vitro dynamically changes the concentrations of ATP and adenosine in extracellular milieu of astrocytic cells. In addition, astrocyte can be regarded as at least one of the target cells of morphine to induce changes of ATP and adenosine levels in central nervous system.

Key words: Morphine; ATP; adenosine; astrocytes

收稿日期：2010-09-19　　录用日期：2010-11-25

通讯作者：刘微　　E-mail: weiliu1980@yahoo.com

引用本文：

刘微, 杨战利, 周乐全, 李小英, 闫福曼, 关莉, 刘海梅, 冯鉴强. 吗啡促进大鼠星形胶质细胞外ATP的酶解和腺苷的生成[J]. 生理学报 2011; 63 (1): 20-24.

LIU Wei, YANG Zhan-Li, ZHOU Le-Quan, LI Xiao-Ying, YAN Fu-Man, GUAN Li, LIU Hai-Mei, FENG Jian-Qiang . Morphine treatment enhances extracellular ATP enzymolysis and adenosine generation in rat astrocytes. Acta Physiol Sin 2011; 63 (1): 20-24 (in Chinese with English abstract).