title: Acetate-dependent mechanisms of inborn tolerance to ethanol.
abstract: OBJECTIVE
  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-СCoA 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Grodno State Medical University, 80 Gorkogo Street, Grodno 230015, Belarus. zimatkin@grsmu.by
authors.forename: Sergey M
authors.initials: SM
authors.lastname: Zimatkin
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Oganesian
authors.forename: Yury V
authors.initials: YV
authors.lastname: Kiselevski
authors.forename: Richard A
authors.initials: RA
authors.lastname: Deitrich
mesh_terms: D000085:Acetates / Q000378:metabolism*; D000105:Acetyl Coenzyme A / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000109:Acetylcholine / Q000032:analysis / Q000235:genetics / Q000502:physiology; D000222:Adaptation, Physiological / Q000235:genetics* / Q000502:physiology; D019973:Alcohol-Related Disorders / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000378:metabolism* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000085:Acetates; D002492:Central Nervous System Depressants; D011768:Pyruvate Dehydrogenase Complex; D000431:Ethanol; D000105:Acetyl Coenzyme A; D000109:Acetylcholine