Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.
Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation.
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DOI：
10.1186/2050-6511-15-62
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发表时间：
2014-11-19
影响因子：
2.9
通讯作者：
Pham TL
中科院分区：
文献类型：
--
作者：
Brosnan RJ;Pham TL
许多麻醉剂调节3-跨膜（如NMDA）和4-跨膜（如GABAA）受体。表现出受体家族特异性的临床和实验麻醉剂通常具有低水溶性。我们假设碳氢化合物的摩尔水溶解度可以用来预测体外受体调节。GABAA（α1β2γ2s）或NMDA（NR 1/NR 2A）受体在卵母细胞中表达，并使用标准双电极电压钳技术进行研究。在饱和浓度下研究了来自14个不同有机官能团的烃，并且每组内的化合物仅在ω-位置或饱和环内的碳数上不同。对GABAA或NMDA受体的影响定义为相对于基线的可逆电流变化≥ 10%，且与零存在统计学差异。烃部分增强GABAA和抑制NMDA受体电流，至少有一些成员从每个功能组调节两种受体类型。NMDA受体的水溶性截止值为1.1 mM，95% CI = 0.45 - 2.8 mM。NMDA受体截止效应与烃链长度或分子体积没有很好的相关性。在所研究的烃的溶解度范围内，未观察到GABAA受体的截止值。烃调节NMDA受体功能表现出摩尔水溶性截止。不相关的受体截止值之间的差异表明，在这些网站的蛋白质-碳氢化合物相互作用的数量，亲和力或疗效可能不同。
Many anesthetics modulate 3-transmembrane (such as NMDA) and 4-transmembrane (such as GABAA) receptors. Clinical and experimental anesthetics exhibiting receptor family specificity often have low water solubility. We hypothesized that the molar water solubility of a hydrocarbon could be used to predict receptor modulation in vitro. GABAA (α1β2γ2s) or NMDA (NR1/NR2A) receptors were expressed in oocytes and studied using standard two-electrode voltage clamp techniques. Hydrocarbons from 14 different organic functional groups were studied at saturated concentrations, and compounds within each group differed only by the carbon number at the ω-position or within a saturated ring. An effect on GABAA or NMDA receptors was defined as a 10% or greater reversible current change from baseline that was statistically different from zero. Hydrocarbon moieties potentiated GABAA and inhibited NMDA receptor currents with at least some members from each functional group modulating both receptor types. A water solubility cut-off for NMDA receptors occurred at 1.1 mM with a 95% CI = 0.45 to 2.8 mM. NMDA receptor cut-off effects were not well correlated with hydrocarbon chain length or molecular volume. No cut-off was observed for GABAA receptors within the solubility range of hydrocarbons studied. Hydrocarbon modulation of NMDA receptor function exhibits a molar water solubility cut-off. Differences between unrelated receptor cut-off values suggest that the number, affinity, or efficacy of protein-hydrocarbon interactions at these sites likely differ.
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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影响因子：
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作者：
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