PT - JOURNAL ARTICLE AU - Valerie B. Caraiscos AU - Robert P. Bonin AU - J. Glen Newell AU - Elzbieta Czerwinska AU - John F. Macdonald AU - Beverley A. Orser TI - Insulin Increases the Potency of Glycine at Ionotropic Glycine Receptors AID - 10.1124/mol.106.033563 DP - 2007 May 01 TA - Molecular Pharmacology PG - 1277--1287 VI - 71 IP - 5 4099 - http://molpharm.aspetjournals.org/content/71/5/1277.short 4100 - http://molpharm.aspetjournals.org/content/71/5/1277.full SO - Mol Pharmacol2007 May 01; 71 AB - The mechanisms by which insulin modulates neuronal plasticity and pain processes remain poorly understood. Here we report that insulin rapidly increases the function of glycine receptors in murine spinal neurons and recombinant human glycine receptors expressed in human embryonic kidney cells. Whole-cell patch-clamp recordings showed that insulin reversibly enhanced current evoked by exogenous glycine and increased the amplitude of spontaneous glycinergic miniature inhibitory postsynaptic currents recorded in cultured spinal neurons. Insulin (1 μM) also shifted the glycine concentration-response plot to the left and reduced the glycine EC50 value from 52 to 31 μM. Currents evoked by a submaximal concentration of glycine were increased to approximately 140% of control. The glycine receptor α subunit was sufficient for the enhancement by insulin because currents from recombinant homomeric α1 receptors and heteromeric α1β receptors were both increased. Insulin acted at the insulin receptor via pathways dependent on tyrosine kinase and phosphatidylinositol 3 kinase because the insulin effect was eliminated by the insulin receptor antagonist, hydroxy-2-naphthalenylmethylphosphonic acid trisacetoxymethyl ester, the tyrosine kinase inhibitor lavendustin A, and the phosphatidylinositol 3 kinase antagonist wortmannin. Together, these results show that insulin has a novel regulatory action on the potency of glycine for ionotropic glycine receptors. The American Society for Pharmacology and Experimental Therapeutics