A positron-emitter labeled glycine(B) site antagonist, [(11)C]L-703,717, preferentially binds to a cerebellar NMDA receptor subtype consisting of GluR epsilon3 subunit in vivo, but not in vitro.
In previous studies, we have found that [(11)C]L-703,717, a positron-emitter labeled antagonist for the glycine-binding site of NMDA receptors, only localizes in rodent cerebellum under in vivo conditions. In order to understand the unusual cerebellar localization, we have examined the binding of [(11)C]L-703,717 to a cerebellar-specific NMDA receptor subtype consisting of GLuRepsilon3 subunit, by comparing its autoradiographic distributions between GluRepsilon3-deficient and wild-type mice. Ex vivo [(11)C]L-703,717 binding to wild-type mice showed a highly specific localization of radioactivity in the cerebellum, whereas that to the GluRepsilon3-deficient mice showed no specific localization of radioactivity in any of the brain regions. In contrast to the ex vivo binding, in vitro [(11)C]L-703,717 binding displayed a similar binding characteristic between GluRepsilon3-deficient and wild-type mice with highly specific localizations in the hippocampus and cerebral cortex. Therefore, the present study clearly demonstrated that [(11)C]L-703,717 preferentially binds to a cerebellar NMDA receptor subtype consisting of GluRepsilon3 subunit in vivo, but not in vitro.
Haradahira
Terushi
T
Division of Medical Imaging, National Institute of Radiological Sciences, Inage-ku, Chiba 263-8555, Japan.
Okauchi
Takashi
T
Maeda
Jun
J
Zhang
Ming-Rong
MR
Kida
Takayo
T
Kawabe
Kouichi
K
Mishina
Masayoshi
M
Watanabe
Yasuyoshi
Y
Suzuki
Kazutoshi
K
Suhara
Tetsuya
T
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002531:Cerebellum / Q000000981:diagnostic imaging*; D004583:Electrons; D005998:Glycine / Q000378:metabolism*; D006912:Hydroxyquinolines / Q000493:pharmacokinetics*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000000981:diagnostic imaging*; D015363:Quinolones / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency* / Q000187:drug effects* / Q000235:genetics
D002250:Carbon Radioisotopes; D006912:Hydroxyquinolines; C119669:L 703717; C432823:NR2C NMDA receptor; D015363:Quinolones; D019275:Radiopharmaceuticals; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine