Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters

1 The effects of ethanol on the Function of recombinant glycine transporter 1 (GLYT1) and glycine transporter 2 (GLYT2) have been investigated. 2 GLYT1b and GLYT2a isoforms stably expressed in hut-nan embryonic kidney 2 93 (HEK 293) cells showed a differential behaviour in the presence of ethan ol, only the GLYT2a isoform was acutely inhibited. 3 The cut-off (alcohols with four carbons) displayed by the n-alkanols on G LYT2a indicates that a specific binding site for ethanol exists on GLYT2a o r on a GLYT2a-interacting protein. 4 The non-competitive inhibition of GLYT2a indicates an allosteric modulati on by ethanol of GLYT2a activity. 5 Chronic treatment with ethanol caused differential adaptive responses on the activity and the membrane expression levels of these transporters. The neuronal GLYT2a isoform decreased in activity and surface expression and th e mainly glial GLYT1b isoform slightly increased in function and surface de nsity. 6 These changes may be involved in some of the modifications of glycinergic or glutamatergic neurotransmitter systems produced by ethanol intoxication .