The effects of ethanol consumption on glutamate production and xCT

Mon, 08/08/2016 - 14:03

xCT is a sodium independent glutamate transporter that regulates the exchange of extracellular l-cystine and intracellular l-glutamate across the plasma membrane. This process is critical to glutathione production and protection from subsequent oxidative stress. Aside from its standard function, xCT participates in a variety of central nervous system (CNS) functions, including formation of the blood–brain barrier, involvement in drug addiction pathways, neurodegeneration caused by lack of oxidative stress protection, and more.  xCT is primarily localized to neurons and glia in the CNS, which is considering its role in glutathione production and efficacy, given that there are an abundance of enzymes and metabolites that can generate reactive oxygen species in these areas.

xct antibody

xCT Antibody [NB300-318] - Detection of xCT in total human and mouse stomach lysate, respectively, using NB300-318. 1 minute ECL exposure.

Alterations in glutamate neurotransmission have been specifically implicated in drug and alcohol abuse.  Rao et al used an xCT antibody to further investigate the role of extra extracellular glutamate in the mesolimbic rewards system and how this correlates with alcohol consumption with exposure to the antibiotic "ceftriaxone".  In their study, rats with exposure to ethanol were given ceftriaxone at doses of 100mg/kg for both 2 and 5 day periods of time.  Using xCT, GLT1, GLT1a and GLT1b antibodies in western blot, they found that a 5-fold increase in ethanol consumption correlated with a highly enhanced expression of these glutamate receptors.  These findings suggest that changes in glutamate levels due to administration of ceftriaxone led to an increase in ethanol consumption. 

Aal-Aaboda et al used an xCT antibody in a similar study aimed at elucidating the role of alcohol consumption and glutamate mediation.  Their preliminary findings showed that alcohol-preferring rats that experienced chronic ethanol consumption (5 weeks) had reduced xCT expression, and that xCT receptor expression increased once alcohol was abstained from.  This led their group to research whether introduction of increased xCT might act as a potential therapeutic method for alcohol dependency.  In order to test this theory, they introduced the synthetic compound MS-153 (R)-(-)-5-methyl-1-nicotinoyl-2-pyrazoline) to a portion of the rats in order to examine receptor level expression.  Using both an xCT and a GLT1 antibody in western blot, their results confirmed that MS-153 increased GLUT1 and xCT receptor expression, which shows the importance of this compound in regulating glutamate receptor activity. 

Overall, these recent studies shed light on a potential new therapeutic approach to alcoholism, where synthetic compounds may have the ability to control glutamate levels in the brain.  This may allow for an individual to decrease the chemical dependency associated with alcoholism by taking a pharmaceutical drug aimed at maintaining glutamate levels. 

Novus Biologicals offers xCT reagents for your research needs including:


  1. PMID: 21564084
  2. PMID: 25619881
  3. PMID: 25601490

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