Different sensitivities of NMDA receptor channel subtypes to non-competitive antagonists.
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.
Yamakura
T
T
Department of Neuropharmacology, Niigata University, Japan.
Mori
H
H
Masaki
H
H
Shimoji
K
K
Mishina
M
M
D000595:Amino Acid Sequence; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009865:Oocytes / Q000378:metabolism; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000235:genetics; D014981:Xenopus
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; C012134:SK&F 10047; D008274:Magnesium; D010620:Phenazocine; D010622:Phencyclidine