In:
Journal of Neurochemistry, Wiley, Vol. 129, No. 2 ( 2014-04), p. 304-314
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‐ 13 C]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‐ 13 C]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‐ 13 C]ethanol with no significant incorporation of 13 C from [1,2‐ 13 C]ethanol into any measured metabolite above natural abundance, although there were measurable effects on total metabolite sizes similar to those seen with unlabelled ethanol. image Ethanol has many documented effects on brain neurochemistry including significantly decreasing glucose consumption. Here, we used multinuclear NMR spectroscopy and metabolomic neuropharmacology to examine alcohol effects on metabolism in cortical brain tissue slices. [1,2‐ 13 C]Ethanol is not metabolized by brain, but very low ethanol [0.1 mM] has significant effects on brain metabolism. Higher ethanol [1.0–60 mM] likely decreases metabolism through action at α4β3δ‐containing GABA(A) receptors.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1111/jnc.2014.129.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2020528-4
SSG:
12
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