Modulation of NMDA receptor by huperzine A in rat cerebral cortex

Modulation of NMDA receptor by huperzine A in rat cerebral cortex 1

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。

AIM: To investigate the effects of huperzine A ( Hup A ) on NMDA receptors in rat cerebral cortex. METHODS: 1) The effect of hup A on NMDA induced current was studied in acutely dissociated rat hippocampal pyramidal neurons using whole cell recording. 2) The effect of Hup A on NMDA receptor binding was assessed using dizocilpine (Diz) binding assay in synaptic membrane preparation of rat cerebral cortex. RESULTS: 1) Hup A reversibly in￣hi￣bit￣ed NMDA induced current in a concentration dependent manner with IC 50 of 45 4 μmol·L -1 . 2) Hup A inhibited the specific binding of MK 801 to extensively washed synaptic membrane of rat cerebral cortex in a con￣cen￣tra￣tion dependent manner with IC 50 of 0 5 (0 1-1 9) μmol·L -1 ( n =4). 3) L Glutamate 10 μmol·L -1 markedly increased MK 801 binding. In the presence of L glutamate, Hup A 0 001-0 1 μmol·L -1 caused a further increase of the binding, whereas Hup A 1-300 μmol·L -1 inhibited the binding in a concentration dependent manner with IC 50 of 12 3 (5 8-26 3) μmol·L -1 ( n =5). CON￣CLU￣SION: Hup A acted as an antagonist of NMDA receptor in cerebral cortex in addition to its inhibitory effect on acetylcholinesterase.