Werner P, Voigt M, Keinänen K, Wisden W, Seeburg P H
Laboratory of Molecular Neuroendocrinology, Centre for Molecular Biology, University of Heidelberg, Germany.
Nature. 1991 Jun 27;351(6329):742-4. doi: 10.1038/351742a0.
Kainic acid is a potent neurotoxin for certain neurons. Its neurotoxicity is thought to be mediated by an excitatory amino-acid-gated ion channel (ionotropic receptor) possessing nanomolar affinity for kainate. 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 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D. 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 greater than quisqualate greater than glutamate much greater than AMPA) with a dissociation constant of about 5 nM for kainate. 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 sites. This correlation, as well as the particular in vivo pattern of neurodegeneration observed on kainate-induced neurotoxicity, suggests that KA-1 participates in receptors mediating the kainate sensitivity of neurons in the central nervous system.
海人酸对某些神经元是一种强效神经毒素。其神经毒性被认为是由一种对海人酸盐具有纳摩尔亲和力的兴奋性氨基酸门控离子通道（离子型受体）介导的。在此，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，它与先前鉴定的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体亚基GluR-A至-D具有30%的序列相似性。在用[³H]海人酸盐进行的结合实验中测定的表达重组KA-1的药理学特征不同于克隆的AMPA受体，并且类似于哺乳动物高亲和力海人酸受体（海人酸盐＞quisqualate＞谷氨酸＞＞AMPA），对海人酸盐的解离常数约为5 nM。KA-1信使RNA在海马体CA3区的选择性高表达与放射自显影定位的高亲和力海人酸结合位点密切对应。这种相关性，以及在海人酸诱导的神经毒性中观察到的特定体内神经退行性变模式，表明KA-1参与介导中枢神经系统中神经元对海人酸敏感性的受体。
