Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Alcohol Alcohol. 2011 May-Jun;46(3):233-8. doi: 10.1093/alcalc/agr014. Epub 2011 Feb 24.

Acetate-dependent mechanisms of inborn tolerance to ethanol.

Author information

  • 1Grodno State Medical University, 80 Gorkogo Street, Grodno 230015, Belarus. zimatkin@grsmu.by

Abstract

AIMS:

To clarify the role of acetate in neurochemical mechanisms of the initial (inborn) tolerance to ethanol.

METHODS:

Rats with low and high inborn tolerance to hypnotic effect of ethanol were used. In the brain region homogenates (frontal and parietal cortex, hypothalamus, striatum, medulla oblongata) and brain cortex synaptosomes, the levels of acetate, acetyl-CoA, acetylcholine (AcH), the activity of pyruvate dehydrogenase (PDG) and acetyl-CoA synthetase were examined.

RESULTS:

It has been found that brain cortex of rats with high tolerance to hypnotic effect of ethanol have higher level of acetate and activity of acetyl-CoA synthetase, but lower level of acetyl-–°CoA and activity of PDG. In brain cortex synaptosomes of tolerant rats, the pyruvate oxidation rate as well as the content of acetyl-CoA and AcH synthesis were lower when compared with intolerant animals. The addition of acetate into the medium significantly increased the AcH synthesis in synaptosomes of tolerant, but not of intolerant animals. Calcium ions stimulated the AcH release from synaptosomes twice as high in tolerant as in intolerant animals. Acetate eliminated the stimulating effect of calcium ions upon the release of AcH in synaptosomes of intolerant rats, but not in tolerant animals. As a result, the quantum release of AcH from synaptosomes in the presence of acetate was 6.5 times higher in tolerant when compared with intolerant rats.

CONCLUSION:

The brain cortex of rats with high inborn tolerance to hypnotic effect of ethanol can better utilize acetate for the acetyl-CoA and AcH synthesis, as well as being resistant to inhibitory effect of acetate to calcium-stimulated release of AcH. It indicates the metabolic and cholinergic mechanisms of the initial tolerance to ethanol.

PMID:
21349883
[PubMed - indexed for MEDLINE]
PMCID:
PMC3114548
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk