H-3 LABELED MK-801 BINDING TO THE EXCITATORY AMINO-ACID RECEPTOR COMPLEX FROM RAT-BRAIN IS ENHANCED BY GLYCINE
H-3 LABELED MK-801 BINDING TO THE EXCITATORY AMINO-ACID RECEPTOR COMPLEX FROM RAT-BRAIN IS ENHANCED BY GLYCINE
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DOI：
10.1073/pnas.84.21.7744
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发表时间：
1987-11-01
影响因子：
11.1
通讯作者：
MILLER, RJ
中科院分区：
文献类型：
--
作者：
REYNOLDS, IJ;MURPHY, SN;MILLER, RJ
本文研究了兴奋性氨基酸拮抗剂~3H标记的MK-801[(+)-5-甲基-10，11-二氢-5H-二苯并[a，d]环己基-5，10-亚胺马来酸]与大鼠脑膜的结合作用。苯环利定、镁离子和3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic酸对~3H标记的MK-801的结合有抑制作用，其抑制作用依赖于L-谷氨酸或N-甲基-D-天冬氨酸，提示它标记了一个与谷氨酸受体的N-甲基-D-天冬氨酸亚型相连的位点。甘氨酸也调节~3H标记的MK-801结合，在0.01-10µm的浓度范围内使其增强。谷氨酸和甘氨酸的作用包括增加结合亲和力，而不改变~3H标记的MK-801结合位点的数目。甘氨酸在该体系中的作用被L-和D-丙氨酸以及L-和D-丝氨酸所模拟。然而，β-丙氨酸和牛磺酸的效果要差得多，而且士的宁不能阻断甘氨酸的作用，这表明它们不是由经典的甘氨酸受体介导的。甘氨酸还增强了N-甲基-D-天冬氨酸增加原代培养的小鼠纹状体神经元钙内流的能力，用钙敏感的荧光染料Fura-2进行了测量。这些结果支持甘氨酸可能是谷氨酸在体内的生理作用的重要调节因素。
We have studied the binding of the excitatory amino acid antagonist 3H-labeled MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate] to extensively washed rat brain membranes. Binding of 3H-labeled MK-801 was inhibited by phencyclidine, Mg2+, and 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid in a manner dependent on the presence of L-glutamate or N-methyl-D-aspartate, suggesting that it labeled a site linked to the N-methyl-D-aspartate subtype of the glutamate receptor. Glycine also regulated 3H-labeled MK-801 binding, enhancing it in the concentration range of 0.01-10 .mu.M. The actions of glutamate and glycine involved increases in binding affinity, without altering the number of 3H-labeled MK-801 binding sites. The effects of glycine in this system were mimicked by L- and D-alanine and L- and D-serine. However, .beta.-alanine and taurine were much less effective, and strychnine did not block the actions of glycine indicating that they were not mediated by the classical glycine receptors. Glycine also enhanced the ability of N-methyl-D-aspartate to increase Ca2+ influx into primary cultures of mouse striatal neurons measured using the Ca2+-sensitive fluorescent dye fura-2. These results support the suggestion that glycine may be an important regulator of the physiological actions of glutamate in vivo.