Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex
Modes of direct modulation by taurine of the glutamate NMDA receptor in rat cortex
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DOI：
10.1016/j.ejphar.2014.01.025
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发表时间：
2014-04-05
影响因子：
5
通讯作者：
Banerjee, Shailesh P.
中科院分区：
文献类型：
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作者：
Chan, Christopher Y.;Sun, Herless S.;Banerjee, Shailesh P.
牛磺酸是一种内源性脑物质，具有强大的神经调节和可能的神经保护特性。虽然已经报道了其他作用机制，但其与NMDA（N-甲基-D-天冬氨酸）受体的相互作用没有记录。我们研究了牛磺酸的相互作用与NMDA受体的电生理和受体结合的方法。测定了牛磺酸对单脉冲电刺激腹内侧皮质诱发的大鼠脑片边缘前皮质第5层场电位反应的影响。印防己毒素（80 μ M）存在于所有对照和药物溶液中以阻断与GABA-、牛磺酸-和士的宁敏感的甘氨酸-受体相关的Cl-通道.典型的反应由NBQX（2，3-二氧代-6-硝基-1，2，3，4-四氢苯并-[f]-喹喔啉-7-磺酰胺）敏感性负波（N1）、随后的正波（P1）和宽负波（N2）组成，两者均对dl-AP 5（dl-2-氨基-5-膦酰基戊酸）抑制敏感。牛磺酸在N2晚期内产生41.5 +/- 8.3%（n=9）电压降低。这种牛磺酸的行动被阻止由100 μ M的AP 5，但不是由10 μ M硝苯地平，支持直接调制的NMDA受体功能的牛磺酸，而不需要参与的L-型Ca 2+通道。在存在甘氨酸或谷氨酸的情况下，牛磺酸未改变[H-3] MK-801与大鼠皮质膜的特异性结合;但在存在甘氨酸的情况下，可抑制精胺增强的[H-3] MK-801与NMDA受体的特异性结合15-20%。此外，牛磺酸降低了10倍的甘氨酸（精胺的存在下）的NMDA受体的表观亲和力。这些结果表明，牛磺酸通过多种机制与NMDA受体直接相互作用。(C)2014爱思唯尔有限公司版权所有。
Taurine is an endogenous brain substance with robust neuromodulatory and possible neuroprotective properties. Though other mechanisms of action have been reported, its interaction with the NMDA (N-methyl-D-aspartic acid) receptor is undocumented. We investigated taurine's interaction with the NMDA receptor using electrophysiological and receptor binding approaches. The effects of taurine on field potential responses in layer-5 of prelimbic cortex in rat brain slices evoked by single-pulse electrical stimulation of ventral medial cortex were determined. Picrotoxin (80 mu M) was present in all control and drug solutions to block the Cl- channels associated with the GABA-, taurine-, and strychnine sensitive glycine- receptors. A typical response consisted of an NBQX (2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo-[f]-quinoxaline-7-sulfonamide)-sensitive negative wave (N1) followed by a positive wave (P1) and a broad negativity (N2), both sensitive to dl-AP5 (dl-2-amino-5-phosphonopentanoic acid) inhibition. Taurine exerted a 41.5 +/- 8.3% (n=9) voltage reduction within the late phase of N2. This taurine action was prevented by 100 mu M AP5, but not by 10 mu M nifedipine, supporting a direct modulation of NMDA receptor function by taurine, without requiring the involvement of the L-type Ca2+ channel. Taurine did not alter specific [H-3] MK-801 binding to rat cortical membranes in the presence of glycine or glutamate; but inhibited spermine-potentiated specific [H-3] MK-801 binding to NMDA receptors by 15-20% in the presence of glycine. In addition, taurine reduced the apparent affinity of the NMDA receptor for glycine (in the presence of spermine) by 10-fold. These results show that taurine interacts directly with the NMDA receptor by multiple mechanisms. (C) 2014 Elsevier B.V. All rights reserved.