PT  - JOURNAL ARTICLE
AU  - Kirson, Dean
AU  - Todorovic, Jelena
AU  - Mihic, S. John
TI  - Positive Allosteric Modulators Differentially Affect Full versus Partial Agonist Activation of the Glycine Receptor
AID  - 10.1124/jpet.112.191486
DP  - 2012 Jul 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 61--70
VI  - 342
IP  - 1
4099  - http://jpet.aspetjournals.org/content/342/1/61.short
4100  - http://jpet.aspetjournals.org/content/342/1/61.full
SO  - J Pharmacol Exp Ther2012 Jul 01; 342
AB  - 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 laevis oocytes was used to compare the enhancing effects of ethanol, anesthetics, and inhalants on human homomeric α1-GlyR activated by saturating concentrations of glycine versus 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 partial agonist.