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Am J Physiol Gastrointest Liver Physiol 280: G1331-G1340, 2001;
0193-1857/01 $5.00
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Vol. 280, Issue 6, G1331-G1340, June 2001

Impairment of H+-K+-ATPase-dependent proton transport and inhibition of gastric acid secretion by ethanol

Juan C. del Valle1,2, María Salvatella1,2, Irma Rossi3, Ramón Andrade1,2, Yolanda Gutiérrez2, Carmen Pereda3, Begoña Samper2, and Juan E. Felíu1,2

1 Department of Biochemistry, Faculty of Medicine, and Departments of 2 Experimental Endocrinology and 3 Gastroenterology, Clínica Puerta de Hierro, Universidad Autónoma de Madrid, E-28029 Madrid, Spain

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 EC50 value of 4.5 ± 0.2%. Ethanol also reduced ATP levels in isolated gastric glands and in cultured parietal cells (EC50: 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 (EC50: 8.5 ± 0.6%), increased passive proton permeability (EC50: 7.9%), and reduced H+-K+-ATPase-dependent proton transport (EC50: 3%). Our results show that the inhibition of gastric acid secretion observed at low concentrations of ethanol (<= 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 >= 7%.

gastric glands; proton permeability; parietal cells


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M. Salvatella, I. Rossi, J. C. Del Valle, Y. Gutierrez, C. Pereda, B. Samper, and J. E. Feliu
Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism
Am J Physiol Gastrointest Liver Physiol, May 1, 2004; 286(5): G711 - G721.
[Abstract] [Full Text] [PDF]


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