D-CYCLOSERINE - A LIGAND FOR THE N-METHYL-D-ASPARTATE COUPLED GLYCINE RECEPTOR HAS PARTIAL AGONIST CHARACTERISTICS
D-CYCLOSERINE - A LIGAND FOR THE N-METHYL-D-ASPARTATE COUPLED GLYCINE RECEPTOR HAS PARTIAL AGONIST CHARACTERISTICS
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DOI：
10.1016/0304-3940(89)90379-0
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发表时间：
1989-03-13
影响因子：
2.5
通讯作者：
MONAHAN, JB
中科院分区：
文献类型：
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作者：
HOOD, WF;COMPTON, RP;MONAHAN, JB
我们之前已经表明，d -环丝氨酸取代[3H]甘氨酸结合到一个与n -甲基- d -天冬氨酸（NMDA）受体调节位点一致的识别位点。此外，d -环丝氨酸正调节NMDA受体，其剂量依赖性增强了[3H]1-[1-（2-噻吩基）环己基]胡椒啶（[3H]TCP）与NMDA受体偶联离子载体的结合。对该化合物的进一步评价表明，d -环丝氨酸对[3H]TCP结合的最大刺激小于作用于NMDA受体相关甘氨酸调节位点（甘氨酸和d -丝氨酸）的其他化合物。此外，在不同固定浓度的甘氨酸存在下，d -环丝氨酸诱导的[3H]TCP结合的刺激导致一系列剂量-反应曲线渐近收敛到甘氨酸单独诱导的最大刺激的40-50%。这些结果与d -环丝氨酸通过与偶联甘氨酸调节位点的相互作用作为NMDA受体的部分激动剂一致。
We have previously shown that D-cycloserine displaces [3H]glycine binding to a recognition site wiht properties consistent with an N-methyl-D-aspartate (NMDA) receptor modulatory site. Additionally, D-cycloserine positively modulates the NMDA receptor as evidenced by its dose-dependent enhancement of [3H]1-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP) binding to the NMDA receptor-coupled ionophore. Further evaluation of this compound indicates that the maximal stimulation of [3H]TCP binding induced by D-cycloserine is lower than that produced by other compounds acting at the NMDA receptor associated glycine modulatory site (glycine and D-serine). Moreover, the stimulation of [3H]TCP binding induced by D-cycloserine in the presence of various fixed concentrations of glycine results in a family of dose-response curves which asymptotically converge to 40-50% of the maximal stimulation induced by glycine alone. These results are consistent with D-cycloserine acting as a partial agonist of the NMDA receptor via its interaction with the coupled glycine modulatory site.