7-氯犬尿氨酸对豚鼠肠肌丛中N-甲基-D-天冬氨酸反应的甘氨酸调节作用

Effect of 7-chloro kynurenic acid on glycine modulation of the N-methyl-D-aspartate response in guinea-pig myenteric plexus.

作者信息

Reggiani A, Maraia G, Ceserani R, Gaviraghi G

机构信息

Glaxo Research Laboratories, Verona, Italy.

出版信息

Eur J Pharmacol. 1989 Sep 1;168(1):123-7. doi: 10.1016/0014-2999(89)90644-4.

DOI:10.1016/0014-2999(89)90644-4

PMID:2511031

Abstract

The glycine modulation of the N-methyl-D-aspartate (NMDA) response in guinea-pig myenteric plexus was investigated by using D-serine and 7-chloro kynurenic acid as a glycine agonist and antagonist, respectively. D-serine caused a concentration-dependent enhancement of the NMDA response, an effect which was competitively inhibited by 7-chloro kynurenic acid (pA2 = 6.0). In addition, 7-chloro kynurenic acid induced a concentration-dependent, non-competitive inhibition of the NMDA response per se, even in the absence of added D-serine. This inhibition was fully reversed by exogenous D-serine, suggesting that this effect was also due to the occupancy of the glycine site. These results emphasize the usefulness of the guinea-pig myenteric plexus for studying the function of the NMDA receptor complex.

摘要

分别使用D-丝氨酸和7-氯犬尿氨酸作为甘氨酸激动剂和拮抗剂，研究了豚鼠肠肌丛中甘氨酸对N-甲基-D-天冬氨酸（NMDA）反应的调节作用。D-丝氨酸引起NMDA反应呈浓度依赖性增强，该效应被7-氯犬尿氨酸竞争性抑制（pA2 = 6.0）。此外，即使在未添加D-丝氨酸的情况下，7-氯犬尿氨酸本身也会引起NMDA反应的浓度依赖性、非竞争性抑制。外源性D-丝氨酸可完全逆转这种抑制作用，表明这种效应也是由于甘氨酸位点被占据所致。这些结果强调了豚鼠肠肌丛在研究NMDA受体复合物功能方面的实用性。