TY - JOUR T1 - Positive allosteric modulators differentially affect full vs. partial agonist activation of the glycine receptor. JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther DO - 10.1124/jpet.112.191486 SP - jpet.112.191486 AU - Dean Kirson AU - Jelena Todorovic AU - S. John Mihic Y1 - 2012/01/01 UR - http://jpet.aspetjournals.org/content/early/2012/04/03/jpet.112.191486.abstract N2 - Taurine acts as a partial agonist at the glycine receptor (GlyR) in some brain regions such as the hippocampus, striatum and nucleus accumbens. Ethanol, volatile anesthetics, and inhaled drugs of abuse are all known positive allosteric modulators of GlyRs, but their effects on taurine-activated GlyRs remain poorly understood, especially their effects on the high concentrations of taurine likely to be found after synaptic release. Two-electrode voltage-clamp electrophysiology in Xenopus oocytes was used to compare the enhancing effects of ethanol, anesthetics, and inhalants on human homomeric α1 GlyR activated by saturating concentrations of glycine vs. taurine. Allosteric modulators had negligible effects on glycine-activated GlyR while potentiating taurine-activated currents. In addition, inhaled anesthetics markedly enhanced desensitization rates of taurine- but not glycine-activated receptors. Our findings suggest that ethanol, volatile anesthetics and inhalants differentially affect the time courses of synaptic events at GlyR, depending on whether the receptor is activated by a full or a partial agonist. ER -