ACTIONS OF D-CYCLOSERINE AT THE N-METHYL-D-ASPARTATE-ASSOCIATED GLYCINE RECEPTOR-SITE INVIVO

被引:104
作者
EMMETT, MR [1 ]
MICK, SJ [1 ]
CLER, JA [1 ]
RAO, TS [1 ]
IYENGAR, S [1 ]
WOOD, PL [1 ]
机构
[1] MONSANTO CO,SEARLE RES & DEV,ST LOUIS,MO 63198
关键词
D-CYCLOSERINE; NMDA; GLYCINE; CEREBELLUM; CGMP;
D O I
10.1016/0028-3908(91)90161-4
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The antibiotic, D-cycloserine has been shown to be a partial agonist at the N-methyl-D-aspartate (NMDA)-coupled, strychnine-insensitive glycine receptor by in vitro receptor binding. This partial agonism was further investigated in an in vivo system, by monitoring changes in levels of cyclic guanosine-monophosphate (cGMP), a well characterized second messenger response, mediated by the NMDA receptor complex, in the cerebellum of the mouse. Parenteral injections of D-cycloserine produced a biphasic dose-response curve which suggested partial agonism. In support of this contention, when intracerebellar injections were made together with D-serine, a glycine agonist, D-cycloserine attenuated the N-methyl-D-aspartate receptor-mediated increase in levels of cGMP. Likewise, systemic administration of D-cycloserine attenuated increases in cGMP induced by pentylenetetrazol. These data are relevant to the study of N-methyl-D-aspartate-mediated neurotransmission, since D-cycloserine is a parenterally bioavailable compound, with both agonist and depressant properties at the N-methyl-D-aspartate-associated glycine receptor.
引用
收藏
页码:1167 / 1171
页数:5
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