KATP开放剂埃他卡林对高K+刺激PC12 细胞释放谷氨酸的影响1

中国临床药理学与治疗学 ›› 2003, Vol. 8 ›› Issue (1): 1-5.

• 研究原著 • 下一篇

K_ATP开放剂埃他卡林对高K⁺刺激PC12 细胞释放谷氨酸的影响¹

姚红红, 张芸, 丁建花, 刘苏怡, 汪海², 胡刚

南京医科大学药理学与神经生物学系, 南京 210029, 江苏; ²军事医学科学院毒物药物研究所, 北京 100850

收稿日期:2002-10-07 修回日期:2002-10-25 发布日期:2020-11-25
通讯作者: 胡刚, 男, 博士, 教授, 博士生导师, 中国药理学会理事, 国家新药审评委员。研究方向:神经精神药理学。Tel:025-6663108 E-mail:ghu@njmu.edu.cn
作者简介:姚红红, 女, 硕士, 讲师。汪海, 男, 博士, 教授, 博士生导师, 国家新药审评委员。研究方向:分子和心脑血管药理学。
基金资助:
1 国家创新药物基础研究重大项目(№969010101)、国家自然科学基金资助项目(№39970846)、教育部优秀青年教师资助计划项目(2001)、教育部高等院校骨干教师资助计划项目(2001) 和江苏省“ 333工程” 基金资助项目

Inhibitory effects and mechanisms of iptkalim on the glutamate release from PC12 cells induced by high K⁺¹

YAO Hong-Hong, ZHANG Yun, DING Jian-Hua, LIU Su-Yi, WANG Hai², HU Gang

Department of Pharmacology and Neurobiology, Nanjing Medical University, Nanjing 210029, Jiangsu; ² Insititute of Pharmacology and Toxicology, Academy of Military Medical Science, Beijing 100850

Received:2002-10-07 Revised:2002-10-25 Published:2020-11-25

摘要/Abstract

摘要： 目的: 研究K_ATP 开放剂埃他卡林(iptkalim,IPT) 对高K⁺刺激PC12 释放谷氨酸(Glu) 的影响及其作用机制。方法: 以培养的PC12 细胞为模型细胞, 应用HPLC 法测定细胞培养液中Glu 含量。结果: IPT 以浓度依赖方式抑制高K⁺刺激PC12 细胞释放Glu, 格列苯脲(Gli) 增强高K⁺刺激PC12 细胞释放Glu 的效应, 并部分逆转IPT 的抑制效应。PKC抑制剂HA-100 和钙调素(CaM) 拮抗剂三氟拉嗪不影响高K⁺刺激PC12 细胞释放Glu, 也不拮抗Gli 的增强效应。结论: IPT 抑制Glu 释放与开放K_ATP 有关,Gli 拮抗IPT 的抑制效应并非由PKC 或CaM 信号传导途径介导。

关键词: 药理学, HPLC, 埃他卡林, ATP 敏感性钾通道, PC12 细胞, 谷氨酸, 格列苯脲, 钙调素

Abstract: AIM: To study the effects and mechanisms of ATP-sensitive potassium channel (K_ATP) opener iptkalim (IPT) on the glutamate release from cultured PC12 cells induced by high K +. METHODS: The glutamate release from cultured PC12 cells was measured by using HPLC combined with fluorescent detector analysis. RESULTS: Different concentrations of IPT (0.01, 0.10, 1.00, 10.0, 100 μmol·L -1) were shown to inhibit glutamate release from PC12 cells induced by high K + in a concentration-dependent manner, and these inhibitory effects were partly reversed by K_ATP blocker glibenclamide (Gli), an inhibitor of K_ATP channel.Incubation with 1.00 μmol·L -1 Gli alone increased the glutamate release induced by high K +, but selective PKC inhibitor HA-100 and calmodulin (CaM) antagonist trifluoperazine failed to affect the increment of glutamate release. CONCLUSION: Inhibition of glutamate release by IPT is partly reversed by Gli, indicating that the effect of IPT is mediated by the opening of the K_ATP channel;PKC and CaM are not involved in the increment of glutamate release by Gli.These results demonstrate that K_ATP channel is implicated in modulating glutamate release.

Key words: pharmacology, HPLC, iptkalim, ATPsensitive potassium channel, PC12 cells, glutamate, calmodulin, glibenclamide

中图分类号:

R971
R966

姚红红, 张芸, 丁建花, 刘苏怡, 汪海, 胡刚. K_ATP开放剂埃他卡林对高K⁺刺激PC12 细胞释放谷氨酸的影响¹[J]. 中国临床药理学与治疗学, 2003, 8(1): 1-5.

YAO Hong-Hong, ZHANG Yun, DING Jian-Hua, LIU Su-Yi, WANG Hai, HU Gang. Inhibitory effects and mechanisms of iptkalim on the glutamate release from PC12 cells induced by high K⁺¹[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2003, 8(1): 1-5.

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K_ATP开放剂埃他卡林对高K⁺刺激PC12 细胞释放谷氨酸的影响¹

Inhibitory effects and mechanisms of iptkalim on the glutamate release from PC12 cells induced by high K⁺¹

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