烟碱对大鼠脑内蛋白激酶A 和C活性的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (1): 44-47.

烟碱对大鼠脑内蛋白激酶A 和C活性的影响

孙秀兰¹, 刘跃, 胡刚¹, 汪海

军事医学科学院毒物药物研究所, 北京 100850;
¹南京医科大学药理学与神经生物学系, 南京 210029, 江苏

收稿日期:2003-07-10 修回日期:2003-08-29 出版日期:2004-01-26 发布日期:2020-11-16
通讯作者: 汪海,男, 研究员, 博士生导师, 主要从事分子药理学研究。Tel:010-66932651 　E-mail: wh@nic.bmi.ac.cn
作者简介:孙秀兰, 女, 博士研究生, 研究方向为神经药理学。E-mail: xiulans@njmu.edu.cn
基金资助:
国家自然科学基金资助项目(NO.30371641)

Influence of nicotine on protein kinase A and protein kinase C activities in the rat brain

SUN Xiu-Lan¹, LIU Yue, HU Gang¹, WANG Hai

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;
¹Department of Pharmacology and Neurobiology, Nangjing Medical University, Nanjing 210029, China

Received:2003-07-10 Revised:2003-08-29 Online:2004-01-26 Published:2020-11-16

摘要/Abstract

摘要： 目的: 观察烟碱对脑内蛋白激酶A 和C 活性的影响。方法: 在烟碱诱导N 受体处于激动态、亚急性失敏、急性失敏和慢性失敏态时, 处死大鼠取全脑匀浆。分别加入PKA 特异性生物素化底物Kemptide和PKC 特异性底物生物素化Neurogranine, 用³²P掺入底物法测定大鼠全脑中蛋白激酶A 和C 的活性。利用基因芯片技术检测慢性失敏时PKA 和PKC 相关基因表达的变化。结果: N 受体激动状态下对PKA 和PKC 的活性没有影响;N 受体亚急性、急性和慢性失敏时使PKA 和PKC 的活性降低。慢性失敏时,PKC Ⅲ基因表达增加, 而PKC 中α、γ、ζ等基因表达没有变化;cAMP 反应元素结合蛋白、cAMP反应元素调节因子、cAMP 磷脂酶、cAMP 依赖性蛋白激酶Ⅱ等6 种基因表达无明显改变。结论: 烟碱作用使N 受体失敏耐受时, 可降低脑内PKA 和PKC的活性, 使脑内信号转导通路发生适应性改变, 这些变化可能是烟碱耐受的重要生化基础。

关键词: 烟碱, 失敏, PKC, PKA, 基因芯片

Abstract: AIM: To determine the effects of nicotine treatment on protein kinase A and protein kinase C activities in the rat brain.METHODS: Treated with nicotine, nicotinic receptors were in activated state, subacute desensitized state, acute desensitized state or chronic desensitized state, respectively. PKA and PKC sample were abstained from the rat whole brain. PKA and PKC activities were assayed by transferring phosphorus (³²P) into the biotinylated peptide Neurogranin and Kemptide, the most specific substrate for PKC and PKA substrates. In addition, using GeneChip to analyze the changes in genes expression of PKC and PKA related proteins after chronic treatment with nicotine.RESULTS: There were no differences in activities of PKA and PKC between control rats and nicotine-treated rats when nicotinic receptors were activated, but PKA and PKC activities were decreased when nicotinic receptors were in subactue, acute or chronic desensitized states induced by nicotine. After chronic treated with nicotine, PKC Ⅲ was up-regulated, and there were 9 transcripts no changed, such as PKC α, γ, ζand CREB, CREM, etc.CONCLUSION: The desensitized nicotinic receptors as a result of nicotine administration, can down-regulate the PKA and PKC activities, and induce the adaptation changes in signal transduction system, which might be responsible for the mechanism of nicotine tolerance.

Key words: nicotine, desensitization, PKA, PKC, GeneChip

中图分类号:

R965

孙秀兰, 刘跃, 胡刚, 汪海. 烟碱对大鼠脑内蛋白激酶A 和C活性的影响[J]. 中国临床药理学与治疗学, 2004, 9(1): 44-47.

SUN Xiu-Lan, LIU Yue, HU Gang, WANG Hai. Influence of nicotine on protein kinase A and protein kinase C activities in the rat brain[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(1): 44-47.

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