Twyman R E, Gahring L C, Spiess J, Rogers S W
Department of Neurology, University of Utah, Salt Lake City 84112, USA.
Neuron. 1995 Apr;14(4):755-62. doi: 10.1016/0896-6273(95)90219-8.
Two rabbits immunized with a portion of glutamate receptor (GluR) subunit GluR3 (amino acids 245-457) exhibited seizure-like behaviors, suggesting that antibodies to GluR3 may modulate neuronal excitability. Using whole-cell recording, rabbit GluR3 antisera were tested on cultured fetal mouse cortical neurons. In a subset of kainate-responsive neurons, miniperfusion of antisera and IgG evoked currents that were blocked by CNQX. Immunoreactivity to synthetic peptides prepared to subregions GluR3A (amino acids 245-274) and GluR3B (amino acids 372-395) was present in both rabbit sera. Peptide GluR3B, but not GluR3A, specifically blocked antisera- and IgG-evoked currents. Similar receptor activation and anti-GluR3 reactivity was present in sera from patients with active Rasmussen's encephalitis, an intractable pediatric epilepsy. Thus, antibodies to GluR3 define a region involved in agonist binding and specific receptor activation. These data suggest that antibodies to neuronal receptors can function as agonists and that autoantibodies to GluRs may be highly specific neurotoxicants in some neurological diseases.
用谷氨酸受体（GluR）亚基GluR3的一部分（氨基酸245 - 457）免疫的两只兔子出现了癫痫样行为，这表明针对GluR3的抗体可能会调节神经元兴奋性。使用全细胞记录法，在培养的胎鼠皮质神经元上测试了兔GluR3抗血清。在一部分对红藻氨酸有反应的神经元中，抗血清和IgG的微量灌注诱发的电流被CNQX阻断。兔血清中均存在对针对GluR3A亚区（氨基酸245 - 274）和GluR3B亚区（氨基酸372 - 395）制备的合成肽的免疫反应性。肽GluR3B而非GluR3A能特异性阻断抗血清和IgG诱发的电流。患有活动性拉斯穆森脑炎（一种难治性小儿癫痫）的患者血清中也存在类似的受体激活和抗GluR3反应性。因此，针对GluR3的抗体确定了一个与激动剂结合和特异性受体激活有关的区域。这些数据表明，针对神经元受体的抗体可以起到激动剂的作用，并且针对GluRs的自身抗体在某些神经疾病中可能是高度特异性的神经毒素。
