司帕沙星、联苯乙酸对大鼠海马神经元GABA-A和离子型谷氨酸受体的作用(英文)  

Effects of sparfloxacin and felbinac on GABA-A and ionotropic glutamate receptors in dissociated rat hippocampal neurons

作　　者：李明华[1] 张莉蓉[2] 王永铭[3] 

机构地区：[1]新乡医学院药理学教研室,河南新乡453003 [2]郑州大学医学院临床药理学教研室,河南郑州450052 [3]复旦大学药学院药理学教研室,上海200032

出　　处：《中国新药与临床杂志》2004年第8期475-479,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：河南省自然科学基金 (0 2 110 4 12 0 0 )~~

摘　　要：目的 :观察司帕沙星单用和与联苯乙酸合用时 ,对γ 氨基丁酸 (GABA) ,NMDA ,AMPA和海人藻酸诱导电流的作用。方法 :应用全细胞式膜片钳技术在急性打散的新生大鼠海马锥体神经元上记录GABA ,NMDA ,AMPA和海人藻酸的诱导电流。结果 :司帕沙星 1mmol·L- 1对GABA诱导的电流有迅速可逆的抑制作用 ,抑制率为 (4 7.6±s2 .9) % ,而联苯乙酸 10 μmol·L- 1无抑制作用。但联苯乙酸 (10 μmol·L- 1)与司帕沙星 1mmol·L- 1合用时 ,稍稍增强抑制作用 ,司帕沙星单用或合用联苯乙酸 (10 μmol·L- 1)对GABA诱导电流的IC50 分别为 (2 38± 2 1) μmol·L- 1和 (89± 5 ) μmol·L- 1。司帕沙星、联苯乙酸或司帕沙星合用联苯乙酸对NM DA ,AMPA和海人藻酸诱导的电流无明显作用。结论 :提示司帕沙星 ,或与联苯乙酸合用时所产生的中枢神经毒性可能与抑制GABA诱导的电流有关 ,而与NMDA ,AMPA和海人藻酸诱导的电流无关。AIM: To examine the effect of the sparfloxacin,alone and in combination with felbinac,on GABA-,NMDA-,AMPA-,and kainite-evoked currents. METHODS: GABA-,NMDA-,AMPA-,and kainite-evoked currents were recorded on dissociated hippocampal neurons of neonatal rat by whole-cell voltage-clamp technique. RESULTS: Spar- floxacin at 1 mmol·L -1 showed reversible rapid suppression on GABA (30 μmol·L -1 )-evoked currents with the rate of (47.6± s 2.9)%. Felbinac 10 μmol·L -1 alone exhibited no suppression but weakly enhanced the inhibitory effect when combined with sparfloxacin 1 mmol·L -1 . IC_ 50 values for sparfloxacin alone and in combination with felbinac on GABA response were (238±21) μmol·L -1 and (89± 5) μmol· L -1 ,respectively. Whole cell currents evoked by NMDA,AMPA or kainite were slightly influenced by sparfloxacin,felbinac,or sparfloxacin plus felbinac. CONCLUSION: These data suggest that the neurotoxicity of sparfloxacin alone or in combination with felbinac may be related to antagonism of GABA-evoked currents but not to an interaction at NMDA-,AMPA-,and kainite-evoked currents.

关 键 词：喹诺酮类 联苯化合物 海马 受体 GA-BA-A 动物 实验 大鼠 司帕沙星 联苯乙酸 

分 类 号：R962[医药卫生—药理学] R978.19[医药卫生—药学]