Ethanol inhibits gastric acid secretion in rats through increased AMP-kinase activity

Cell Physiol Biochem. 2010;25(2-3):195-202. doi: 10.1159/000276553. Epub 2010 Jan 12.

Abstract

The effects of ethanol on gastric acid secretion remain controversial. The present study examines the effect of low-dose (2%) short term (15-20 min) ethanol exposure on gastric acid secretion via a potential interaction with AMP-activated protein kinase (AMPK). Real-time fluorescence digital imaging was used to provide functional evidence for the interaction of ethanol and AMPK in modulating secretagogue-induced acid secretion. Individual rat gastric glands were loaded with the pH-sensitive dye BCECF and the secretagogues carbachol (200 microM) or histamine (200 microM) were added to induce secretion. Rates of pH recovery were calculated as DeltapH(i)/Deltat. In one series of experiments, secretagogue-induced acid secretion was inhibited by 2% ethanol, or the AMPK activator AICAR monophosphate (AICAR) (20 mM). In a separate series, 2% ethanol was added in combination with compound C (20 microM), an AMPK inhibitor, to prevent activation of AMPK. 2% ethanol significantly suppressed stimulated acid secretion. In order to confirm modulation of AMPK activity by ethanol, the specific AMPK inhibitor compound C was used, which reversed the inhibitory effects of ethanol on stimulated acid secretion. This study demonstrates that low dose ethanol (2%) inhibits secretagogue-dependent acid secretion by activation of the AMPK pathway in rat gastric parietal cells.

MeSH terms

  • AMP-Activated Protein Kinases / antagonists & inhibitors
  • AMP-Activated Protein Kinases / metabolism*
  • Aminoimidazole Carboxamide / analogs & derivatives
  • Aminoimidazole Carboxamide / pharmacology
  • Animals
  • Carbachol / pharmacology
  • Ethanol / pharmacology*
  • Fluoresceins / chemistry
  • Fluorescent Dyes / chemistry
  • Gastric Acid / metabolism*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Histamine / pharmacology
  • Hydrogen-Ion Concentration
  • Hypoglycemic Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Ribonucleotides / pharmacology

Substances

  • Fluoresceins
  • Fluorescent Dyes
  • Hypoglycemic Agents
  • Ribonucleotides
  • Aminoimidazole Carboxamide
  • Ethanol
  • Histamine
  • 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
  • Carbachol
  • AMP-Activated Protein Kinases
  • AICA ribonucleotide