人脑N-甲基-D-天冬氨酸受体亚基的分子克隆、功能表达及药理学特性
Molecular cloning, functional expression, and pharmacological characterization of an N-methyl-D-aspartate receptor subunit from human brain.
作者信息
Planells-Cases R, Sun W, Ferrer-Montiel A V, Montal M
机构信息
Department of Biology, University of California, San Diego, La Jolla 92093-0319.
出版信息
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5057-61. doi: 10.1073/pnas.90.11.5057.
A cDNA encoding a full-length N-methyl-D-aspartate (NMDA) receptor subunit 1, hNR1, was isolated from a human brain cDNA library. The hNR1 cDNA encodes an open reading frame of approximately 2.7 kb that shares high homology with the rat brain NMDA receptor subunit 1 and the mouse zeta 1 subunit. The hNR1 sequence, however, diverges from the rodent and murine homologs near the C terminus, suggesting that they represent alternatively spliced messages of the same gene. Oocytes injected with cRNA synthesized from the hNR1 cDNA express glutamate and NMDA-activated currents in the presence of glycine. Currents are blocked by the NMDA-receptor-specific antagonists 2-amino-5-phosphovaleric acid and 7-chlorokynurenate, and the open channel blockers MK-801 and phencyclidine, by Mg2+ ions in a voltage-dependent manner, and by Zn2+. Expressed hNR1 homomeric receptor channels exhibit the high Ca2+ permeability characteristic of neuronal NMDA receptors. Therefore, the cDNA clone hNR1 codes for a human brain NMDA receptor subunit cognate to the rodent and murine brain NR1 subunits.
从人脑cDNA文库中分离出一个编码全长N-甲基-D-天冬氨酸（NMDA）受体亚基1（hNR1）的cDNA。hNR1 cDNA编码一个约2.7 kb的开放阅读框，与大鼠脑NMDA受体亚基1和小鼠ζ1亚基具有高度同源性。然而，hNR1序列在C末端附近与啮齿动物和小鼠的同源物不同，表明它们代表同一基因的可变剪接信息。注射了由hNR1 cDNA合成的cRNA的卵母细胞在甘氨酸存在下表达谷氨酸和NMDA激活电流。电流被NMDA受体特异性拮抗剂2-氨基-5-磷酸缬氨酸和7-氯犬尿氨酸、开放通道阻滞剂MK-801和苯环利定、Mg2+离子以电压依赖性方式以及Zn2+阻断。表达的hNR1同聚体受体通道表现出神经元NMDA受体的高Ca2+通透性特征。因此，cDNA克隆hNR1编码一种与人脑NMDA受体亚基同源的啮齿动物和小鼠脑NR1亚基。
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