Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10767093 | Biochemical and Biophysical Research Communications | 2007 | 5 Pages |
Abstract
Bis(7)-tacrine has been shown to prevent glutamate-induced neuronal apoptosis by blocking NMDA receptors. However, the characteristics of the inhibition have not been fully elucidated. In this study, we further characterize the features of bis(7)-tacrine inhibition of NMDA-activated current in cultured rat hippocampal neurons. The results show that with the increase of extracellular pH, the inhibitory effect decreases dramatically. At pH 8.0, the concentration-response curve of bis(7)-tacrine is shifted rightwards with the IC50 value increased from 0.19 ± 0.03 μM to 0.41 ± 0.04 μM. In addition, bis(7)-tacrine shifts the proton inhibition curve rightwards. Furthermore, the inhibitory effect of bis(7)-tacrine is not altered by the presence of the NMDA receptor proton sensor shield spermidine. These results indicate that bis(7)-tacrine inhibits NMDA-activated current in a pH-dependent manner by sensitizing NMDA receptors to proton inhibition, rendering it potentially beneficial therapeutic effects under acidic conditions associated with stroke and ischemia.
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Authors
Jialie Luo, Wenming Li, Yuwei Liu, Wei Zhang, Hongjun Fu, Nelson T.K. Lee, Hua Yu, Yuanping Pang, Pingbo Huang, Jun Xia, Zhi-Wang Li, Chaoying Li, Yifan Han,