Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters.
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.
Núñez
E
E
Departamento de Biologia Molecular, Centro de Biologia Molecular 'Severo Ochoa', Facultad de Ciencias, Universidad Autonoma de Madrid, 28049-Madrid, Spain.
López-Corcuera
B
B
Martínez-Maza
R
R
Aragón
C
C
D000438:Alcohols / Q000633:toxicity; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005998:Glycine / Q000378:metabolism / Q000493:pharmacokinetics*; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D007700:Kinetics; D020033:Protein Isoforms; D017981:Receptors, Neurotransmitter / Q000378:metabolism / Q000502:physiology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects
D000438:Alcohols; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050487:Glycine Plasma Membrane Transport Proteins; D020033:Protein Isoforms; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; C493271:SLC6A5 protein, human; C493268:SLC6A9 protein, human; D000431:Ethanol; D005998:Glycine