Modulation of the NMDA receptor by polyamines.
Modulation of the NMDA receptor by polyamines.
复制标题
多胺对 NMDA 受体的调节。
DOI：
10.1016/0024-3205(91)90463-l
复制
发表时间：
1991
期刊：
影响因子：
6.1
通讯作者：
Molinoff,PB
中科院分区：
文献类型：
--
作者：
Williams,K;Romano,C;Dichter,MA;Molinoff,PB
最近的生物化学和电生理学研究结果表明，多胺的识别位点作为NMDA受体复合物的一部分存在。该位点似乎与先前描述的谷氨酸、甘氨酸、Mg++、Zn++和开放通道阻滞剂（如MK-801）的结合位点不同。内源性多胺精胺和亚精胺增加开放通道阻滞剂的结合，并增加NMDA引起的电流在培养的神经元。这些多胺被称为多胺识别位点的激动剂。研究天然和合成多胺对[3 H]MK-801结合和培养神经元中NMDA诱导电流的影响，鉴定出多胺识别位点的部分激动剂、拮抗剂和反向激动剂。还发现多胺影响配体与谷氨酸和甘氨酸的识别位点的结合。然而，这些影响可能是介导的网站不同的多胺的作用，以调节开放通道阻滞剂的结合。内源性多胺可能通过作用于NMDA受体的多胺识别位点来调节兴奋性突触传递。该位点可能代表用于治疗缺血诱导的神经毒性、癫痫和神经退行性疾病的新的治疗靶点。
Results of recent biochemical and electrophysiological studies have suggested that a recognition site for polyamines exists as part of the NMDA receptor complex. This site appears to be distinct from previously described binding sites for glutamate, glycine, Mg++, Zn++, and open-channel blockers such as MK-801. The endogenous polyamines spermine and spermidine increase the binding of open-channel blockers and increase NMDA-elicited currents in cultured neurons. These polyamines have been termed agonists at the polyamine recognition site. Studies of the effects of natural and synthetic polyamines on the binding of [3H]MK-801 and on NMDA-elicited currents in cultured neurons have led to the identification of compounds classified as partial agonists, antagonists, and inverse agonists at the polyamine recognition site. Polyamines have also been found to effect the binding of ligands to the recognition sites for glutamate and glycine. However, these effects may be mediated at a site distinct from that at which polyamines act to modulate the binding of open-channel blockers. Endogenous polyamines may modulate excitatory synaptic transmission by acting at the polyamine recognition site of the NMDA receptor. This site could represent a novel therapeutic target for the treatment of ischemia-induced neurotoxicity, epilepsy, and neurodegenerative diseases.