In vitro and in vivo characterization of the NMDA receptor-linked strychnine-insensitive glycine site
Modulation of the NMDA receptor by the strychnine-insensitive glycine site was studied both in vitro and in vivo. In vitro the glycinergic stimulation of [ 3H]MK801 binding was measured in three different rat forebrain membrane preparations. An increased association rate of [ 3H]MK801 in the presenc...
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Published in | Epilepsy research Vol. 12; no. 2; pp. 157 - 162 |
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Main Authors | , |
Format | Journal Article Conference Proceeding |
Language | English |
Published |
Amsterdam
Elsevier B.V
01.07.1992
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | Modulation of the NMDA receptor by the strychnine-insensitive glycine site was studied both in vitro and in vivo. In vitro the glycinergic stimulation of [
3H]MK801 binding was measured in three different rat forebrain membrane preparations. An increased association rate of [
3H]MK801 in the presence of glycine was observed. The binding of the radioligand was also enhanced by
d-serine, whereas
l-serine was less potent. The concentration-effect curves were shifted to the right by the glycine antagonist 7-chlorokynurenic acid (7CKA). In vivo modulation of the
N-
methyl-
d-aspartate
(NMDA) receptor was studied using NMDA induced convulsions in 7 day old rats. The NMDA effect was blocked by (+)-5-methyl-10,11-dihydro-
5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801) and
d-(-)-2-amino-5-phosphono-pentanoic acid (AP5). The effect of a submaximal dose of NMDA was dose-dependently potentiated by 1–10 mg/kg
d-serine, whereas higher doses of
l-serine were needed to obtain a similar effect. 7CKA did not affect NMDA-induced convulsions but reduced the
d-serine potentiation of NMDA responses. This study illustrates the ability of the strychnine-insensitive glycine site to modulate the NMDA receptor function both in vitro and in vivo. |
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ISSN: | 0920-1211 1872-6844 |
DOI: | 10.1016/0920-1211(92)90036-S |