Modulation of NMDA receptor by huperzine A in rat cerebral cortex

• 作 者: 王晓东 张景明 杨惠华 胡国渊
• 机 构: 中国科学院上海药物研究所
• 出 处: Acta Pharmacologica Sinica
• 发表日期: 1999年01期
• 关键词: 马来酸盐 结合量 cortex 大脑皮层突触膜 膜片箝 NMDA 受体拮抗剂 胆碱酯酶抑制剂 锥体细胞 石杉碱甲

目的：研究石杉碱甲（ＨｕｐＡ）对大脑皮层ＮＭＤＡ受体的影响．方法：１）用急性分离海马锥细胞全细胞记录研究ＨｕｐＡ对ＮＭＤＡ诱发电流的影响．２）用大脑皮层突触膜标本研究ＨｕｐＡ对［３Ｈ］Ｄｉｚ特异性结合的影响．结果：１）ＨｕｐＡ可逆地抑制ＮＭＤＡ诱发的电流反应（ＩＣ５０＝４５４μｍｏｌ·Ｌ－１）．２）在突触膜标本，ＨｕｐＡ抑制［３Ｈ］Ｄｉｚ的结合量（ＩＣ５０＝０５（０１－１９）μｍｏｌ·Ｌ－１，ｎ＝４）．３）Ｌ谷氨酸１０μｍｏｌ·Ｌ－１增加［３Ｈ］Ｄｉｚ结合量．加入Ｌ谷氨酸后，ＨｕｐＡ０００１－０１μｍｏｌ·Ｌ－１进一步增加结合量；ＨｕｐＡ１－３００μｍｏｌ·Ｌ－１则抑制结合量（ＩＣ５０＝１２３（５８－２６３）μｍｏｌ·Ｌ－１，ｎ＝５）．结论：ＨｕｐＡ在大脑皮层除了抑制乙酰胆碱酯酶外，还是ＮＭＤＡ受体拮抗剂

Objective: To study the effect of HupA on NMDA receptor in cerebral cortex. Methods: 1) The effects of HupA on NMDA-induced currents were investigated by whole-cell recording of acutely isolated hippocampal pyramidal cells. 2) Studying the effect of HupA on [3H] Diz-specific binding using synaptic membrane samples of cerebral cortex. Results: 1) HupA reversibly inhibited the NMDA-induced current response (IC50 = 45.4μmol·L-1). 2) In the synaptic membrane samples, HupA inhibited the binding of [3H] Diz (IC50 = 05 (01-19) μmol·L-1, n = 4). 3) L-glutamic acid 10 μmol·L-1 increased [3H] Diz binding. After adding L-glutamic acid, HupA0001-01μmol·L-1 further increased the binding amount; HupA1-300μmol·L-1 inhibited the binding amount (IC50 = 123 (58-263) μmol·L-1, n = 5). Conclusion: In addition to inhibiting acetylcholinesterase in the cerebral cortex, HupA is also an NMDA receptor antagonist