N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents.
N-methyl-D-aspartate receptors: different subunit requirements for binding of glutamate antagonists, glycine antagonists, and channel-blocking agents.
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发表时间：
1994-03
影响因子：
3.6
通讯作者：
David A. Lynch;N. Anegawa;T. Verdoorn;Dolan B. Pritchett
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文献类型：
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作者：
David A. Lynch;N. Anegawa;T. Verdoorn;Dolan B. Pritchett
爪蟾卵母细胞中 NR-1 亚基的表达产生对谷氨酸做出反应的通道，并被 N-甲基-D-天冬氨酸 (NMDA) 受体的竞争性和非竞争性拮抗剂阻断。与 NR-2 受体亚基共表达可增加通过这些通道的离子电导。我们表征了由转染细胞中表达的亚基组合组装而成的 NMDA 受体的药理学特性，以确定通过配体结合实验检测到的竞争性谷氨酸拮抗剂、甘氨酸拮抗剂和通道阻断剂结合的最低亚基要求。 NR-1a 的单独表达产生甘氨酸拮抗剂结合，而 NR-1a 和 NR-2A 的组合需要产生谷氨酸拮抗剂和通道阻断剂的结合位点。这些结果表明功能性 NMDA 受体由这些亚基组装而成。然而，NMDA 和多胺的药理作用差异表明，并非天然 NMDA 受体的所有特征都能通过这种亚基组合重现。
Expression of the NR-1 subunit in Xenopus oocytes produces channels that respond to glutamate and are blocked by competitive and noncompetitive antagonists of the N-methyl-D-aspartate (NMDA) receptor. Ionic conductances through these channels are increased by coexpression with NR-2 receptor subunits. We have characterized the pharmacological properties of NMDA receptors assembled from combinations of subunits expressed in transfected cells, to determine the minimum subunit requirements for binding of competitive glutamate antagonists, glycine antagonists, and channel-blocking agents, as detected by ligand-binding experiments. Expression of NR-1a alone produced glycine antagonist binding, whereas the combination of NR-1a and NR-2A was needed to produce binding sites for glutamate antagonists and channel-blocking agents. These results suggest that functional NMDA receptors assemble from these subunits. However, differences in the pharmacological effects of NMDA and polyamines show that not all characteristics of native NMDA receptors are reproduced by this combination of subunits.