【摘 要】
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Bis(7)-tacrine has been shown to prevent glutamate-induced neuronal apoptosis by blocking NMDA receptors.However,the characteristics of the inhibition have
【机 构】
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Department of Biochemistry, Hong Kong University of Science and Technology, Kowloon, Hong Kong, Chin
【出 处】
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中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
论文部分内容阅读
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.In addition,bis(7)-tacrine shifts the proton inhibition curve rightwards.It was further observed that alkalinization slows the onset of bis(7)-tacrine inhibition,and reduces the potency of bis(7)-tacrine.Furthermore,the inhibitory effect of bis(7)-tacirne 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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