The influence of bicarbonate ions on the GABA-mimetic activity of ethylenediamine
The influence of bicarbonate ions on the GABA-mimetic activity of ethylenediamine
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碳酸氢根离子对乙二胺 GABA 模拟活性的影响
DOI：
10.1016/0028-3908(85)90174-1
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发表时间：
1985
影响因子：
4.7
通讯作者：
D. Hill
中科院分区：
文献类型：
--
作者：
D. Hill
用放射配基结合法和体外组织培养法研究了乙二胺和哌嗪在哺乳动物γ-氨基丁酸受体上的拟GABA活性。在Tris-Buffers和Krebs-Henseleit溶液(KHS)中，测定乙二胺和哌嗪作为GABA受体与大鼠脑突触膜结合的拮抗剂的效力。如果使用Krebs-Henseleit溶液进行测定，乙二胺和哌嗪在GABA上的效价和乙二胺在GABA受体上的效价都会提高。哌嗪对GABA受体无活性。Krebs-Henseleit的GABA受体拮抗剂荷包牡丹碱在Krebs-Henseleit中的效力也高于Tris-柠檬酸盐缓冲液。在Krebs-Henseleit中存在的离子中，重碳酸盐离子是乙二胺和哌嗪类GABA效价增加的原因。将NaHCO3或KHCO3(25 MM)加入Tris-HCl缓冲液(用于GABA结合)或Tris-HCl+2.5 mM CaCl2(用于GABA结合)中，所得IC50值与在Krebs-Henseleit溶液中测得的IC50值相似。在该体系中，碳酸氢根离子还能增强乙二胺增强[~3H]地西潘与大鼠脑膜结合的能力(提高乙二胺的效力和最大效应)。在无HCO3-−离子存在的情况下，乙二胺通过提高受体的最大结合容量(Bmax)而不改变受体的亲和力(Kd)来增强[~3H]地西潘的结合。碳酸氢钾(25 MM)通过改变Bmax和Kd使乙二胺进一步增强[~3H]安定的结合力。从灌流分离的大鼠颈上神经节的溶液中去除HCO3GABA离子可消除对乙二胺的去极化反应，但不影响对−或蝇草酚的去极化反应。结论：乙二胺和哌嗪的GABA模拟活性依赖于碳酸氢根离子的生理浓度。
A study was performed to investigate the GABA-mimetic activity of ethylenediamine (EDA) and piperazine at mammalian γ-aminobutyric acid (GABA) receptors using radioligand binding assays andin vitroisolated tissues. The potency of ethylenediamine and piperazine as inhibitors of the binding of GABA receptors to synaptic membranes from rat brain was measured in Tris-buffers and Krebs-Henseleit solution (KHS). The potency of ethylenediamine and piperazine at GABAAand ethylenediamine at GABABreceptors was raised if Krebs-Henseleit solution was used for the assay. Piperazine was inactive at GABABreceptors. The potency of the antagonist of GABAAreceptors bicuculline methobromide, was also increased in Krebs-Henseleit when compared with Tris-citrate buffer. Of the ions present in Krebs-Henseleit, bicarbonate ions were responsible for the increase in the GABA-mimetic potency of ethylenediamine and piperazine. Addition of either NaHCO3or KHCO3(25 mM) to Tris-HCl buffer (for GABAAbinding) or Tris-HCl plus 2.5 mM CaCl2(for GABABbinding) yielded IC50values similar to those measured in Krebs-Henseleit solution. Bicarbonate ions also enhanced the ability of ethylenediamine to potentiate the binding of [3H]diazepam to membranes from rat brain (raising both the potency of ethylenediamine and its maximum effect) in this system. In the absence of HCO3−ions, ethylenediamine potentiated the binding of [3H]diazepam by raising the maximum binding capacity (Bmax) without changing the affinity (Kd) of the receptors. Potassium bicarbonate (25 mM) caused ethylenediamine to further potentiate the binding of [3H]diazepam by changing bothBmaxand Kd. Removal of HCO3−ions from solutions superfusing isolated superior cervical ganglia of the rat abolished the depolarizing response to ethylenediamine without affecting that to GABA or muscimol. It is concluded that the GABA-mimetic activity of ethylenediamine and piperazine is dependent upon physiological concentrations of bicarbonate ions.