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机构地区:[1]军事医学科学院毒物药物研究所,北京100850
出 处:《中国药理学与毒理学杂志》2004年第4期264-268,共5页Chinese Journal of Pharmacology and Toxicology
摘 要:目的 探讨一氧化氮合酶抑制剂左旋硝基精氨酸甲酯 (L NAME)、N 甲基 D 天冬氨酸 (NMDA)受体拮抗剂地佐环平 (MK 80 1)和钙通道阻滞剂硝苯地平对吗啡作用的影响是否与细胞 [Ca2 + ]i 有关。方法 体外培养NG10 8 15细胞 ,用荧光指示剂Fura2 AM负载 ,荧光分光光度计动态测定细胞 [Ca2 + ]i。结果 吗啡、MK 80 110 μmol·L- 1、硝苯地平 1,2和3μmol·L- 1急性处理能降低由NMDA刺激 (模拟兴奋性刺激 )所致的细胞 [Ca2 + ]i 升高。MK 80 110μmol·L- 1和硝苯地平 3μmol·L- 1与吗啡合用均能完全对抗NMDA的作用。吗啡处理细胞 4 8h后 ,再用纳洛酮处理 ,细胞 [Ca2 + ]i 可增加约 39% ,L NAME ,MK 80 1和硝苯地平与吗啡合用均能降低纳洛酮引起的细胞 [Ca2 + ]i 的升高。结论 MK 80 1,L NAME和硝苯地平对吗啡调节的作用均与胞内Ca2 +AIM To explore if the influence of N ω nitro L arginine methyl ester (L NAME, nitric oxide synthase inhibitor), dizocilpine 〔MK 801, N methyl D aspartate (NMDA) receptor antagonist〕 and nifedipine (calcium channel blocker) on the action of morphine is mediated by variation of intracellular calcium concentration ([Ca 2+ ] i). METHODS The [Ca 2+ ] i of NG108 15 cells cultured in vitro was measured dynamically with fluorospectrophotometer after treated with fluorescent probe Fura2 AM. RESULTS The increases in [Ca 2+ ] i induced by NMDA treatment (simulating the excitatory stimulation) were inhibited by morphine or MK 801 10 μmol·L -1 or nifedipine 3 μmol·L -1 acute treatment, and inhibited completely by MK 801 10 μmol·L -1 or nifedipine 3 μmol·L -1 cotreated with morphine. After having been treated with morphine for 48 h, the cells were then treated with naloxone, the [Ca 2+ ] i overshooting by 39% approximately. These overshoots induced by naloxone could be blocked by L NAME, MK 801 or nifedipine cotreated with morphine. CONCLUSION The modulation with morphine effects by L NAME, MK 801 and nifedipine was related to the variation of [Ca 2+ ] i.
关 键 词:钙 细胞内 细胞 NG108.15 吗啡 左旋 硝基精氨酸甲酯 地佐环平 硝苯地平 N-甲基-D- 天冬氨酸
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