Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells
Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells
复制标题
主要在海马 CA3 细胞中表达的推定高亲和力红藻氨酸受体的克隆
作者：
P. Werner;M. Voigt;K. Keinänen;W. Wisden;P. Seeburg
海人酸对某些神经元是一种有效的神经毒素1。它的神经毒性被认为是由兴奋性氨基酸门控离子通道（离子型受体）介导的，对红藻氨酸具有纳摩尔亲和力2。在这里，我们描述了大鼠兴奋性氨基酸受体基因家族的一个新成员，KA-1，它与先前表征的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluR-A至-D3-5具有30%的序列相似性。在与[3 H]红藻氨酸盐的结合实验中确定的表达的重组KA-1的药理学特征不同于克隆的AMPA受体的药理学特征，并且类似于哺乳动物高亲和力红藻氨酸盐受体（红藻氨酸盐>使君子酸盐>谷氨酸盐> AMPA），对于红藻氨酸盐的解离常数为约5 nM 2，6。海马CA 3区KA-1信使RNA的选择性高表达与放射自显影定位的高亲和力红藻氨酸结合位点密切相关7 -9。这种相关性，以及在红藻氨酸诱导的神经毒性1，2上观察到的神经变性的特定体内模式，表明KA-1参与介导中枢神经系统中神经元的红藻氨酸敏感性的受体。
KAINIC acid is a potent neurotoxin for certain neurons1. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate2. Here we describe a new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D3–5. The pharmacological profile of expressed recombinant KA-1 determined in binding experiments with [3H]kainate is different from that of the cloned AMPA receptors and similar to the mammalian high-affinity kainate receptor (kainate > quisqualate > glutamate » AMPA) with a dissociation constant of about 5 nM for kainate2,6. The selectively high expression of KA-1 messenger RNA in the CA3 region of the hippocampus closely corresponds to autoradiographically located high-affinity kainate binding sites7–9. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity1,2, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.