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 alpha1 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.
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 alpha1 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.
Authors: Lindsay M McCracken; James R Trudell; Beth E Goldstein; R Adron Harris; S John Mihic Journal: Neuropharmacology Date: 2009-11-11 Impact factor: 5.250
Authors: Moonnoh R Lee; David J Hinton; Jinhua Wu; Prasanna K Mishra; John D Port; Slobodan I Macura; Doo-Sup Choi Journal: Neurosci Lett Date: 2010-12-21 Impact factor: 3.046