Ethanol, Not Detectably Metabolized in Brain, Significantly Reduces Brain Metabolism, Probably via Action at Specific GABA(A) Receptors and Has Measureable Metabolic Effects at Very Low Concentrations

J Neurochem. 2014 Apr;129(2):304-14. doi: 10.1111/jnc.12634. Epub 2013 Dec 18.

Abstract

Ethanol is a known neuromodulatory agent with reported actions at a range of neurotransmitter receptors. Here, we measured the effect of alcohol on metabolism of [3-¹³C]pyruvate in the adult Guinea pig brain cortical tissue slice and compared the outcomes to those from a library of ligands active in the GABAergic system as well as studying the metabolic fate of [1,2-¹³C]ethanol. Analyses of metabolic profile clusters suggest that the significant reductions in metabolism induced by ethanol (10, 30 and 60 mM) are via action at neurotransmitter receptors, particularly α4β3δ receptors, whereas very low concentrations of ethanol may produce metabolic responses owing to release of GABA via GABA transporter 1 (GAT1) and the subsequent interaction of this GABA with local α5- or α1-containing GABA(A)R. There was no measureable metabolism of [1,2-¹³C]ethanol with no significant incorporation of ¹³C from [1,2-¹³C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabelled ethanol.

Keywords: 13C metabolism; GABA(A); NMR spectroscopy; alcohol; metabonomics.

MeSH terms

  • Animals
  • Brain / metabolism*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Ethanol / metabolism
  • Ethanol / pharmacology*
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Pattern Recognition, Automated
  • Principal Component Analysis
  • Pyruvic Acid / metabolism
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism*

Substances

  • Ligands
  • Receptors, GABA-A
  • Ethanol
  • Pyruvic Acid