美金刚胺对重组鼠NMDA受体表达的影响HEK 293个细胞。

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Bresink我Benke助教,Collett VJ,密封AJ,帕森斯CG,亨利JM, Collingridge GL

美金刚胺对重组鼠NMDA受体表达的影响HEK 293个细胞。

Br J杂志。1996年9月,119 (2):195 - 204。

PubMed ID

8886398 (在PubMed

]

文摘

1。竞争力的行动n -甲基- d(门冬氨酸)受体拮抗剂、美金刚胺(1-amino-3 5-dimethyladamantane)和(+)mk - 801 ((+) 5-methyl-10 11-dihydro-5H-dibenzo [a, d] cyclohepten-5 10-imine马来酸,dizocilpine),在重组NMDA受体研究利用全细胞膜片箝技术。2。人类胚胎肾HEK 293细胞是暂时性的转染不同NMDA受体亚基组合(NR1a / NR2A, NR1a / NR2B和NR1a / NR2D)。突变形式的绿色荧光蛋白(GFP)与NMDA受体亚基cotransfected启用转染细胞的可视化。3所示。美金刚胺(0.3 -30 microM)阻塞L-glutamate (100 microM)浓度的方式调节电流在NR1a / NR2A, NR1a / NR2B和NR1a / NR2D转染细胞的IC50值(-70 mV) 0.93 + / - 0.15 microM, 0.82 + / - 0.12 microM和0.47 + / - 0.06 microM(平均+ / -南卡罗莱纳州的意思),分别。4所示。memantine-induced块强烈压敏电阻器。变更持有潜在的-70 mV + 60 mV导致了e-fold IC50值每增加30-33 mV膜电位的变化,对所有3亚基组合调查。 5. The kinetics of the actions of memantine (30 microM) were investigated for the NR1a/2A combination, in 6 cells (13-15 determinations). At -70 mV, the block and recovery from block were both best described by two exponentials with time-constants of 201 +/- 23 ms (81 +/- 2%) and 3.9 +/- 0.6 s and 597 +/- 94 ms (18 +/- 1%) and 18.6 +/- 2.4 s, respectively. The predominant effect of depolarization was to increase the weight of the faster recovery time-constant. Kinetic analysis suggests that these results are consistent with previously proposed Markov models. 6. (+)-MK-801 was studied briefly for comparative purposes. (+)-MK-801 (200 nM) preferentially blocked NMDA receptor currents (at -70 mV) in NR1a/NR2A and NR1a/NR2B (82 +/- 10% and 93 +/- 2% depressions) compared to NR1a/NR2D (38 +/- 7%) transfected cells. (+)-MK-801 appeared to be less voltage-dependent than memantine on all three receptor combinations. 7. In conclusion, memantine was a voltage-dependent antagonist of recombinant rat NMDA receptors expressed in HEK 293 cells but showed little selectivity between the subunits investigated. Its actions on these recombinant receptor combinations are similar to its actions on native NMDA receptors.

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药物靶点

药物	目标	类	生物	药理作用	行动
谷氨酸	谷氨酸受体ionotropic, NMDA 2 a	蛋白质	人类	未知的	不可用	细节
谷氨酸	谷氨酸受体ionotropic, NMDA 2 d	蛋白质	人类	未知的	不可用	细节