Subunit-specific modulation of [ 3H]MK-801 binding to NMDA receptors mediated by dopamine receptor ligands in rodent brain

WigestrandM.B.; FonnumF.; IvarWalaasS.

首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Subunit-specific modulation of [ 3H]MK-801 binding to NMDA receptors mediated by dopamine receptor ligands in rodent brain

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Subunit-specific modulation of [ 3H]MK-801 binding to NMDA receptors mediated by dopamine receptor ligands in rodent brain

机译：多巴胺受体配体介导的啮齿动物脑中[3H] MK-801与NMDA受体结合的亚基特异性调节

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Dopamine D1 receptor (D1R) ligands may directly interact with the NMDA receptor (NMDAR), but detailed knowledge about this effect is lacking. Here we identify D1R ligands that directly modulate NMDARs and examine the contributions of NR2A and NR2B subunits to these interactions. Binding of the open channel blocker [ 3H]MK-801 in membrane preparations from rat- and mouse brain was used as a biochemical measure of the functional state of the NMDAR channel. We show that both D1R agonist A-68930 and dopamine receptor D2 antagonist haloperidol can decrease [ 3H]MK-801 binding with increased potency in membranes from the NR2A -/- mice (i.e. in membranes containing NR2B only), as compared to the inhibition obtained in wild-type membranes. Further, a wide range of D1R agonists such as A-68930, SKF-83959, SKF-83822, SKF-38393 and dihydrexidine were able to decrease [ 3H]MK-801 binding, all showing half maximal inhibitory concentrations ～20 μM, and with significant effects occurring at or above 1 μM. With membranes from D1R -/- mice, we demonstrate that these effects occurred through a D1R-independent mechanism. Our results demonstrate that dopamine receptor ligands can selectively influence NR2B containing NMDARs, and we characterize direct inhibitory NMDAR effects by different D1R ligands.

机译：多巴胺D1受体（D1R）配体可能直接与NMDA受体（NMDAR）相互作用，但缺乏有关这种作用的详细知识。在这里，我们确定直接调节NMDARs的D1R配体，并检查NR2A和NR2B亚基对这些相互作用的贡献。在大鼠和小鼠脑膜制剂中，开放通道阻滞剂[3H] MK-801的结合被用作NMDAR通道功能状态的生化指标。我们显示，与抑制作用相比，D1R激动剂A-68930和多巴胺受体D2拮抗剂氟哌啶醇均可降低[3H] MK-801结合，并增强NR2A-/-小鼠膜（即仅包含NR2B的膜）的效力。在野生型膜中获得。此外，广泛的D1R激动剂，例如A-68930，SKF-83959，SKF-83822，SKF-38393和二氢己定能够降低[3H] MK-801结合，均显示最大抑制浓度的一半为〜20μM，并且在1μM或更高的浓度下产生显着影响。用来自D1R-/-小鼠的膜，我们证明了这些作用是通过D1R独立机制发生的。我们的结果表明，多巴胺受体配体可以选择性地影响含有NR2B的NMDAR，并且我们通过不同的D1R配体来表征直接抑制NMDAR的作用。

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《Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry》 |2012年第2期|共11页
作者
WigestrandM.B.; FonnumF.; IvarWalaasS.;
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正文语种 eng
中图分类生物化学;
关键词
D1 receptor; Dopamine; Interaction; MK-801; NMDA receptor; SKF-38393;

机译：D1受体;多巴胺;相互作用;MK-801;NMDA受体;SKF-38393;

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1. Subunit-specific modulation of [ 3H]MK-801 binding to NMDA receptors mediated by dopamine receptor ligands in rodent brain [J] . WigestrandM.B., FonnumF., IvarWalaasS. Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry . 2012,第2期

机译：多巴胺受体配体介导的啮齿动物脑中[3H] MK-801与NMDA受体结合的亚基特异性调节
2. Treatment with 1,2,3,4,-tetrahydroisoquinoline affects glutamate release in the striatum but not the binding of (3H)MK-801 to NMDA receptors in the dopaminergic structures of the rat brain. [J] . Lorenc Koci E, Golembiowska K, Pietraszek M, Pharmacological reports: PR . 2009,第5期

机译：用1,2,3,4，-四氢异喹啉处理会影响纹状体中的谷氨酸释放，但不会影响（3H）MK-801与大鼠脑多巴胺能结构中NMDA受体的结合。
3. Treatment with 1,2,3,4,-tetrahydroisoquinoline affects glutamate release in the striatum but not the binding of [3H]MK-801 to NMDA receptors in the dopaminergic structures of the rat brain. [J] . El?bieta Lorenc-Koci, Krystyna Go?embiowska, Ma?gorzata Pietraszek, Pharmacological reports: PR . 2009,第5期

机译：用1,2,3,4，-四氢异喹啉处理会影响纹状体中的谷氨酸释放，但不会影响[3H] MK-801与大鼠脑多巴胺能结构中NMDA受体的结合。
4. Hypofunction of NMDA Receptors Due to the Hyperactivation of Dopamine Receptors in the Hippocampal Synapses of Schizophrenia Based on a Mathematical Model [C] . Ali Mahdavi, Fariba Bahrami, Mina Mirjalili, Iranian Conference on Biomedical Engineering . 2015

机译：基于数学模型的精神分裂症海马突触中的多巴胺受体血管活化，NMDA受体的紊乱
5. Dopamine D(1A) receptor-deficient mice: An examinaton of D(1)-like receptors in rodent brain. [D] . Montague, Deidra Moneta. 1999

机译：多巴胺D（1A）受体缺陷型小鼠：啮齿动物脑中D（1）样受体的检查。
6. A Role for Adenosine A1 Receptors in GABA and NMDA-Receptor Mediated Modulation of Dopamine Release: Studies Using Fast Cyclic Voltammetry [O] . John J. O′Connor, Carmel O′Neill 2008

机译：腺苷A1受体在GABA和NMDA受体介导的多巴胺释放调节中的作用：使用快速循环伏安法的研究
7. Reduction of NMDA receptors with dithiothreitol increases [3H]-MK-801 binding and NMDA-induced Ca2+ fluxes. [O] . Reynolds, I. J., Rush, E. A., Aizenman, E. 1990

机译：用二硫苏糖醇还原NMDA受体可增加[3H] -MK-801结合和NMDA诱导的Ca2 +通量。

Subunit-specific modulation of [ 3H]MK-801 binding to NMDA receptors mediated by dopamine receptor ligands in rodent brain

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