Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor

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• 作者：Megan E. Tipps¹ ; Sangeetha V. Iyer ; S. John Mihic ; ^{mihic@mail.utexas.edu}
• 关键词：Anesthetic metabolism ; Allosteric modulation ; Glycine receptor ; GABAA receptor ; 5-HT3 receptor ; Trifluoroacetate
• 刊名：Neuropharmacology
• 出版年：2012
• 期刊代码：33_00283908
• 类别：pha
• 出版时间：September, 2012
• 卷：63
• 期：3
• 页码：368-373
• 文件大小：469 K

摘要

Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in聽vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABA_A and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate.

Trifluoroacetate (100 渭M-3 mM) enhanced the currents elicited by low concentrations of glycine applied to 伪1 homomeric and 伪1尾 heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on 伪1尾2纬2S GABA_A or 5-HT3A receptors at any GABA or serotonin concentration tested.

The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control.