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Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters
Author(s) -
Núñez Enrique,
LópezCorcuera Beatriz,
MartínezMaza Rodrigo,
Aragón Carmen
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703100
Subject(s) - glycine , gene isoform , biochemistry , transporter , glycine receptor , chemistry , neurotransmitter transporter , ethanol , hek 293 cells , glutamatergic , biology , microbiology and biotechnology , amino acid , receptor , glutamate receptor , gene
The effects of ethanol on the function of recombinant glycine transporter 1 (GLYT1) and glycine transporter 2 (GLYT2) have been investigated. GLYT1b and GLYT2a isoforms stably expressed in human embryonic kidney 293 (HEK 293) cells showed a differential behaviour in the presence of ethanol; only the GLYT2a isoform was acutely inhibited. The ‘cut‐off’ (alcohols with four carbons) displayed by the n‐alkanols on GLYT2a indicates that a specific binding site for ethanol exists on GLYT2a or on a GLYT2a‐interacting protein. The non‐competitive inhibition of GLYT2a indicates an allosteric modulation by ethanol of GLYT2a activity. 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 the mainly glial GLYT1b isoform slightly increased in function and surface density. These changes may be involved in some of the modifications of glycinergic or glutamatergic neurotransmitter systems produced by ethanol intoxication.British Journal of Pharmacology (2000) 129 , 802–810; doi: 10.1038/sj.bjp.0703100