Yamakura T, Mori H, Masaki H, Shimoji K, Mishina M
Department of Neuropharmacology, Niigata University, Japan.
Neuroreport. 1993 Jun;4(6):687-90. doi: 10.1097/00001756-199306000-00021.
Four kinds of heteromeric N-methyl-D-aspartate (NMDA) receptor channels, the epsilon 1/zeta 1, epsilon 2/zeta 1, epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, were expressed in Xenopus oocytes and their sensitivities to various non-competitive antagonists were examined. The epsilon 1/zeta 1 and epsilon 2/zeta 1 channels were more sensitive to (+)MK-801 (dizocilpine) than the epsilon 3/zeta 1 and epsilon 4/zeta 1 channels, whereas the sensitivities to phencyclidine (PCP), ketamine and N-allylnormetazocine (SKF-10,047) were only slightly variable among the four epsilon/zeta channels. Furthermore, the replacement by glutamine or arginine of the conserved asparagine residue in segment M2 of the epsilon 2 and zeta 1 NMDA receptor channel subunits reduced the sensitivities to PCP, ketamine and SKF-10,047, though to different extents. These results, together with previous findings, suggest that these non-competitive antagonists as well as (+)MK-801 and Mg2+ act on a common site.
四种异聚体N-甲基-D-天冬氨酸（NMDA）受体通道，即ε1/ζ1、ε2/ζ1、ε3/ζ1和ε4/ζ1通道，在非洲爪蟾卵母细胞中表达，并检测了它们对各种非竞争性拮抗剂的敏感性。ε1/ζ1和ε2/ζ1通道比ε3/ζ1和ε4/ζ1通道对（+）MK-801（地卓西平）更敏感，而在这四种ε/ζ通道中，对苯环己哌啶（PCP）、氯胺酮和N-烯丙基去甲唑啉（SKF-10,047）的敏感性只有轻微差异。此外，用谷氨酰胺或精氨酸取代ε2和ζ1 NMDA受体通道亚基M2片段中保守的天冬酰胺残基，会降低对PCP、氯胺酮和SKF-10,047的敏感性，不过降低程度不同。这些结果与先前的发现一起表明，这些非竞争性拮抗剂以及（+）MK-801和Mg2+作用于一个共同位点。
