| Effects of （-）-stepholidine on NMDA receptors： comparison with haloperidol and clozapine |
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| 引用本文： | Gu WH,Yang S,Shi WX,Zhen XC,Jin GZ. Effects of （-）-stepholidine on NMDA receptors： comparison with haloperidol and clozapine[J]. Acta pharmacologica Sinica, 2007, 28(7): 953-958 |
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| 作者姓名： | Gu WH Yang S Shi WX Zhen XC Jin GZ |
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| 作者单位： | [1]Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China [2]Neuropsychopharmacological Research Unit, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA |
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| 基金项目： | Projects supported by the Ministry of Science and Technology （№ 973-2003CB51 54000） and the National Natural Science Foundation of China （№ 30230130 and 30572168）. |
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| 摘 要： | Aim： To examine whether （-）-stepholidine （SPD） has a direct effect on the N- methyl-D-aspartic acid receptors （NMDAR） containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol （Hal） and clozapine （Cloz）. Methods： NMDAR was transiently expressed in human embryonic kidney 293 （HEK293） cells. Changes in intracellular calcium concentration （[Ca^2＋]i） induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. Results： SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 μmol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NRI a/NR2B receptor-mediated Ca^2＋ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. Conclusion： Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D1 receptor action underlying an indirect mechanism.
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| 关 键 词： | 镇定剂 氟哌啶醇 NMDA受体 钙成像 |
| 修稿时间： | 2006-09-262007-01-24 |
Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine |
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| Gu Wei-hua,Yang Shen,Shi Wei-xing,Zhen Xue-chu,Jin Guo-zhang. Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine[J]. Acta pharmacologica Sinica, 2007, 28(7): 953-958 |
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| Authors: | Gu Wei-hua Yang Shen Shi Wei-xing Zhen Xue-chu Jin Guo-zhang |
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| Affiliation: | Department of Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China. |
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| Abstract: | AIM: To examine whether (-)-stepholidine (SPD) has a direct effect on the N-methyl- D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). METHODS: NMDAR was transiently expressed in human embryonic kidney 293 (HEK293) cells. Changes in intracellular calcium concentration ([Ca2+]i) induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. RESULTS: SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 micromol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NR1a/NR2B receptor-mediated Ca2+ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. CONCLUSION: Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D1 receptor action underlying an indirect mechanism. |
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