Ethanol inhibits gastric acid secretion in rats through increased AMP-kinase activity.
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.
Kopic
Sascha
S
Department of Surgery, Yale University, School of Medicine, New Haven, CT 06511, USA.
Corradini
Stefanie
S
Sidani
Shafik
S
Murek
Michael
M
Vardanyan
Artur
A
Föller
Michael
M
Ritter
Markus
M
Geibel
John P
JP
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005452:Fluoresceins / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism / Q000473:pathology; D006632:Histamine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology
D005452:Fluoresceins; D005456:Fluorescent Dyes; D007004:Hypoglycemic Agents; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000431:Ethanol; D006632:Histamine; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D002217:Carbachol; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide