CLONING OF A CDNA FOR A GLUTAMATE RECEPTOR SUBUNIT ACTIVATED BY KAINATE BUT NOT AMPA
CLONING OF A CDNA FOR A GLUTAMATE RECEPTOR SUBUNIT ACTIVATED BY KAINATE BUT NOT AMPA
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DOI：
10.1038/351745a0
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发表时间：
1991-06-27
期刊：
影响因子：
64.8
通讯作者：
HEINEMANN, S
中科院分区：
文献类型：
--
作者：
EGEBJERG, J;BETTLER, B;HEINEMANN, S
脊椎动物中枢神经系统的快速兴奋性传递主要由L-谷氨酸介导。根据药理、生理和激动剂的结合特性，离子亲性谷氨酸受体可分为N-甲基-D-天冬氨酸(N-甲基-D-天冬氨酸)、AMPADNA和红藻氨酸亚型1。编码非N-甲基-D-天冬氨酸受体亚基的互补(alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate)克隆之间的序列同源性显示至少有两个亚基类型：GluR_1-GluR_4类2-6和GluR_5类7。由GluR1-GluR4类产生的受体对AMPA的表观亲和力高于对海人藻酸3-6的表观亲和力。在非洲爪哇卵母细胞中表达时，均聚体GluR6受体可被红藻氨酸、Quisqualate和L-谷氨酸激活，但不被AMPA激活，并且与红藻氨酸的表观亲和力高于对GluR1-GluR4受体的亲和力。持续应用激动剂观察受体的脱敏作用。同源GluR6谷氨酸受体呈现向外整流的电流-电压关系。原位杂交显示GluR6基因的表达模式与[H-3]红藻氨酸的结合模式相似。
FAST excitatory transmission in the vertebrate central nervous system is mediated mainly by L-glutamate. On the basis of pharmacological, physiological and agonist binding properties, the ionotropic glutamate receptors are classified into NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate) and kainate subtypes 1. Sequence homology between complementary DNA clones encoding non-NMDA glutamate receptor subunits reveals at least two subunit classes: the GluR1 to GluR4 class 2-6 and the GluR5 class 7. Here we report the cloning and expression of a functional rat glutamate receptor subunit cDNA, GluR6, which has a very different pharmacology from that of the GluR1-GluR4 class. Receptors generated from the GluR1-GluR4 class have a higher apparent affinity for AMPA than for kainate 3-6. When expressed in Xenopus oocytes the homomeric GluR6 receptor is activated by kainate, quisqualate and L-glutamate but not by AMPA, and the apparent affinity for kainate is higher than for receptors from the GluR1-GluR4 class. Desensitization of the receptor was observed with continuous application of agonist. The homomeric GluR6 glutamate receptor exhibits an outwardly rectifying current-voltage relationship. In situ hybridizations reveal a pattern of GluR6 gene expression reminiscent of the binding pattern obtained with [H-3]kainate.