Impairment of H+-K+-ATPase-dependent proton transport and inhibition of gastric acid secretion by ethanol.
Ethanol (1-20% vol/vol) caused a dose-dependent reduction in the basal rate of acid formation in isolated rabbit gastric glands with a calculated EC(50) value of 4.5 +/- 0.2%. Ethanol also reduced ATP levels in isolated gastric glands and in cultured parietal cells (EC(50): 8.8 +/- 0.4% and 8.5 +/- 0.2%, respectively) and decreased both basal and forskolin-stimulated cAMP levels. In studies carried out in gastric gland microsomes, ethanol inhibited the hydrolytic activity of H+-K+-ATPase(EC(50): 8.5 +/- 0.6%), increased passive proton permeability (EC(50): 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC(50): 3%). Our results show that the inhibition of gastric acid secretion observed at low concentrations of ethanol (< or =5%) is mainly caused by the specific impairment of H+-K+-ATPase-dependent proton transport across cell membranes rather than inhibition of the hydrolytic activity of H+-K+-ATPase, reduction in the cellular content of ATP, or increase in the passive permeability of membranes to protons, although these changes, in combination, must be relevant at concentrations of ethanol > or =7%.
del Valle
J C
JC
Department of Biochemistry, Faculty of Medicine, Clínica Puerta de Hierro, Universidad Autónoma de Madrid, E-28029 Madrid, Spain.
Salvatella
M
M
Rossi
I
I
Andrade
R
R
Gutiérrez
Y
Y
Pereda
C
C
Samper
B
B
Felíu
J E
JE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004396:Coloring Agents / Q000493:pharmacokinetics; D000242:Cyclic AMP / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017506:H(+)-K(+)-Exchanging ATPase / Q000502:physiology*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D010539:Permeability; D011522:Protons; D011817:Rabbits; D014343:Trypan Blue / Q000493:pharmacokinetics
D004396:Coloring Agents; D011522:Protons; D000431:Ethanol; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D017506:H(+)-K(+)-Exchanging ATPase; D014343:Trypan Blue