Straight-chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits
Straight-chain alcohols exhibit a cutoff in potency for the inhibition of recombinant glutamate receptor subunits
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DOI：
10.1038/sj.bjp.0704112
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发表时间：
2001-07-01
影响因子：
7.3
通讯作者：
Akinshola, BE
中科院分区：
文献类型：
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作者：
Akinshola, BE
1采用双电极电压钳记录技术研究了正构醇(甲醇至正己醇)对非洲爪哇卵母细胞海人藻酸激活的AMPA受体亚单位GluR1和GluR3离子电流的影响。2对于从甲醇到正己醇的短链醇，其抑制GluR1和GluR3受体介导的电流的能力随醇的链长或疏水性的增加而增加。GluR3的IC50值为：甲醇，712 mm；乙醇，238 mm；正丙醇，50 mm；正丁醇，32 mm；正戊醇，13 mm；对于长链醇，正庚醇的抑制作用弱于正己醇(IC(50)：GluR1为19 mM，G1uR3为18 mM)，正辛醇仅对GluR3影响不大，1-正庚醇和1-正十一醇对GluR1和GluR3反应均无明显抑制作用。正醇抑制非NMDA谷氨酸受体功能的截断值与醇通过与受体蛋白上特定尺寸的乙醇结合部位相互作用而影响这些受体通道功能的解释是一致的。
1 The effects of n-alcohols (methanol to 1-decanol) on kainate-activated AMPA receptor subunit GluR1 and GluR3 ion currents were studied in Xenopus oocytes using the two-electrode voltage-clamp recording technique.2 For short-chain alcohols from methanol to 1-hexanol, potency for inhibition of GluR1 and GluR3 receptor-mediated current increased in proportion to the chain length or hydrophobicity of the alcohol.3 The IC50 values of these alcohols for GluR1 were: methanol, 702 mM; ethanol, 170 mM; 1-propanol, 69 mM; 1-butanol, 20 mM; 1-pentanol, 17 mM; and 1-hexanol, 10 mM. For GluR3, IC50 values were: methanol, 712 mM; ethanol, 238 mM; 1-propanol, 50 mM; 1-butanol, 32 mM; 1-pentanol, 13 mM; and 1-hexanol, 7 mM.4 For long-chain alcohols, 1-heptanol was less potent than 1-hexanol (estimated iC(50): 19 mM for GluR1 and 18 mM for G1uR3), 1-octanol had little effect only on GluR3, and 1-nonanol and 1-decanol did not significantly inhibit both GluR1 and GluR3 responses.5 The observations indicate that straight-chain n-alcohols exhibit a cutoff in their potency for inhibition of the function of non-NMDA glutamate receptor subunits, GluR1 and G1uR3. The cutoff in potency of n-alcohols for inhibition of non-NMDA glutamate receptor function is consistent with the interpretation that alcohols affect the function of these receptor-channels by interacting with an alcohol binding site of specific dimensions on the receptor protein.