Ethanol enhances taurine-activated glycine receptor function.
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.


CONCLUSIONS
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.
Welsh
Brian T
BT
Institutes for Neuroscience, University of Texas at Austin, Austin, Texas 78712, USA.
Kirson
Dean
D
Allen
Hunter M
HM
Mihic
S John
SJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D018009:Receptors, Glycine / Q000235:genetics / Q000502:physiology*; D013654:Taurine / Q000494:pharmacology*; D014981:Xenopus; D015032:Zinc / Q000502:physiology
D018009:Receptors, Glycine; D013654:Taurine; D000431:Ethanol; D015032:Zinc; D005998:Glycine; C100184:tricine