强啡肽对培养脊髓神经元高钾刺激性胞内钙增高的双向作用  

Dualistic effect of dynorphin on high potassium- induced increase of intracellular free calcium concentration in cultured rat spinal neurons

作　　者：胡文辉[1,2] 张翠华[1,2] 杨惠芬[1,2] 郑永芳 刘娜[1,2] 孙秀君 任民峰[1,2] 

机构地区：[1]中国医学科学院中国协和医科大学基础医学研究所 [2]第三军医大学野战外科研究所

出　　处：《中国药理学与毒理学杂志》1998年第1期32-35,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金

摘　　要：为探讨强啡肽（Ｄｙｎ）镇痛与致瘫的细胞机理，采用Ｆｕｒａ－２显微荧光光度技术观测了不同浓度的ＤｙｎＡ（１－１７）对原代培养脊髓神经元单个细胞内游离钙离子浓度（［Ｃａ２＋］ｉ）的影响．ＤｙｎＡ０．１－１００μｍｏｌ·Ｌ－１对基础［Ｃａ２＋］ｉ均无影响．ＤｙｎＡ０．１和１μｍｏｌ·Ｌ－１使高钾（５０ｍｍｏｌ·Ｌ－１）刺激的Ｃａ２＋内流峰值反应分别下降９４％（ｎ＝６）和８３％（ｎ＝４，Ｐ＜０．０５）；ＤｙｎＡ１０和１００μｍｏｌ·Ｌ－１对高钾刺激反应峰值无明显影响，但所有测试细胞均呈现持续性［Ｃａ２＋］ｉ升高；预先给予低浓度的ＤｙｎＡ（０．１和１μｍｏｌ·Ｌ－１），则高浓度ＤｙｎＡ（１０和１００μｍｏｌ·Ｌ－１）的促进作用明显减弱甚至消失．结果表明低浓度和高浓度ＤｙｎＡ（１－１７）对培养脊髓神经元的基础［Ｃａ２＋］ｉ无影响，但可分别抑制和促进去极化性钙离子内流，低浓度ＤｙｎＡ可对抗高浓度ＤｙｎＡ的促进作用．In order to explore the cellular mechanisms for dynorphin (Dyn) spinal analgesia and neurotoxicity, the effects of various concentrations of Dyn A(1-17) on the high potassiuminduced increase in free intracellular calcium concentration([Ca2+]i) were studied in rat spinal neuron primary culture with single cell microspectrofluorimetry. Dyn A(1-17) 0.1-100 μmol·L1 had no significant effect on the basal [Ca2+]i. Dyn 0.1 and 1 μmol·L1 significantly decreased the peak [Ca2+]i evoked with high potassium (KCl 50 mmol·L1) by 94% and 83% respectively. With Dyn A(1-17) 10 and 100 μmol·L1, the regular increase in peak [Ca2+]i was sustained following high potassium challenge and showed no recovery throughout the observation period. Serial addition of graded low to high concentrations of Dyn A(1-17) 0.1, 1, 10 and 100 μmol·L1 failed to produce the sustained rise of peak [Ca^2+]i following potassium depolarization in the presence of high concentration of Dyn A(1-17) alone. These results suggested that in the cultured rat spinal neurons Dyn A(1-17) have an inhibitory effect on the depolarizationevoked calcium influx at low concentrations and an enhancing effect at high concentrations. In addition, serial addition of graded concentrations of Dyn A(1-17) antagonized the enhancing effect of high concentration of Dyn A(1-17) on the calcium influx.

关 键 词：强啡肽 脊髓 神经元 钙 

分 类 号：R971[医药卫生—药品]