Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha(7)-neuronal receptors and neuronal CNS receptors
Nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha(7)-neuronal receptors and neuronal CNS receptors
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DOI：
10.1016/s0006-8993(97)00556-8
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发表时间：
1997-08-08
期刊：
影响因子：
2.9
通讯作者：
Kimura, J
中科院分区：
文献类型：
--
作者：
Kaneko, S;Maeda, T;Kimura, J
我们利用原代培养的大鼠皮质神经元，研究了尼古丁对谷氨酸诱导的细胞毒性的影响。细胞活力在谷氨酸作用10min后与无谷氨酸培养液孵育1h后显著下降，在谷氨酸作用前8~24h加入尼古丁(10mM)可明显减轻谷氨酸诱导的细胞毒性，而单独尼古丁对细胞活力无明显影响。尼古丁的神经保护作用依赖于潜伏期。α-银环蛇毒素(α-BTX)和甲基乌头碱(MLA)都是α(7)-神经元受体拮抗剂，二氢-β-红景天碱(DHβE)是神经中枢神经系统(CNS)受体拮抗剂，它们都能显著拮抗尼古丁对谷氨酸诱导的细胞毒性的保护作用。钙离子载体离子霉素和一氧化氮(NO)供体S亚硝半胱氨酸也以类似谷氨酸的方式诱导细胞毒性。尼古丁对离子霉素诱导的细胞毒性有保护作用，但对SNOC诱导的细胞毒性无保护作用。这些结果表明，尼古丁通过α(7)神经元受体和神经元中枢神经系统受体保护培养的大脑皮层神经元免受谷氨酸诱导的细胞毒性，其机制是通过减少钙内流引发的NO生成。(C)1997年爱思唯尔科学公司。
We examined the effects of nicotine on glutamate-induced cytotoxicity using primary cultures of rat cortical neurons. The cell viability decreased significantly when cultures were exposed to glutamate for 10 min and then incubated with glutamate-free medium for 1 h. The exposure of cultures to nicotine (10 mu M) for 8-24 h prior to glutamate application ameliorated the glutamate-induced cytotoxicity, with no significant effect of nicotine alone on the cell viability. Neuroprotection by nicotine was dependent on the incubation period. alpha-bungarotoxin (alpha-BTX) and methyllycaconitine (MLA), both of which are alpha(7)-neuronal receptor antagonists, and dihydro-beta-erythroidine (DH beta E), a neuronal central nervous system (CNS) receptor antagonist, each significantly antagonized the protection by nicotine against glutamate-induced cytotoxicity. Ionomycin, a calcium ionophore, and S-nitrosocysteine (SNOC), a nitric oxide (NO) donor, also induced cytotoxicity in a manner similar to glutamate. Nicotine protected cultures against ionomycin-induced cytotoxicity, but not against SNOC-induced cytotoxicity. These results suggest that nicotine protects cultured cortical neurons against glutamate-induced cytotoxicity via alpha(7)-neuronal receptors and neuronal CNS receptors by reducing NO-formation triggered by Ca2+ influx. (C) 1997 Elsevier Science B.V.