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Ethanol Enhances Taurine‐Activated Glycine Receptor Function
Author(s) -
Welsh Brian T.,
Kirson Dean,
Allen Hunter M.,
Mihic S. John
Publication year - 2010
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2010.01249.x
Subject(s) - taurine , glycine , glycine receptor , ethanol , chemistry , function (biology) , receptor , microbiology and biotechnology , biochemistry , biology , amino acid
Background: Emerging evidence suggests that taurine acts as a partial agonist on glycine receptors (GlyR) in vitro and in vivo. Ethanol acts as an allosteric modulator on the GlyR producing a leftward shift of the glycine concentration–response curve, with no enhancing effects observed at saturating glycine concentrations. However, to date, no electrophysiological studies have been performed on ethanol modulation of taurine‐activated GlyR. Methods: Wild‐type α1 GlyR, or those bearing a serine‐267 to isoleucine replacement (S267I), were homomerically expressed in Xenopus oocytes and voltage clamped at −70 mV. Ethanol was co‐applied with varying concentrations of glycine or taurine and the enhancing effects of ethanol compared. Results: Ethanol potentiated glycine‐ and taurine‐activated GlyR responses in a concentration‐dependent manner. It shifted taurine and glycine concentration–response curves to the left, having no effects at saturating agonist concentrations. Chelation of zinc by tricine decreased ethanol enhancement of taurine‐gated GlyR function. The S267I mutation prevented ethanol enhancement of taurine‐mediated responses as previously also reported for glycine. Conclusion: Ethanol modulates taurine activation of GlyR function by a mechanism similar to that of the full agonist glycine. The lack of effect of ethanol at saturating taurine concentrations provides mechanistic information on alcohol actions at the GlyR.