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Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases

The mechanism by which pancreas secretes high HCO(3) (-) has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO(3) (-) from serosa to mucosa or by moving H(+) in the opposite direction. The aim of the present study was to determine wheth...

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Autores principales: Wang, Jing, Barbuskaite, Dagne, Tozzi, Marco, Giannuzzo, Andrea, Sørensen, Christiane E., Novak, Ivana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436373/
https://www.ncbi.nlm.nih.gov/pubmed/25993003
http://dx.doi.org/10.1371/journal.pone.0126432
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author Wang, Jing
Barbuskaite, Dagne
Tozzi, Marco
Giannuzzo, Andrea
Sørensen, Christiane E.
Novak, Ivana
author_facet Wang, Jing
Barbuskaite, Dagne
Tozzi, Marco
Giannuzzo, Andrea
Sørensen, Christiane E.
Novak, Ivana
author_sort Wang, Jing
collection PubMed
description The mechanism by which pancreas secretes high HCO(3) (-) has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO(3) (-) from serosa to mucosa or by moving H(+) in the opposite direction. The aim of the present study was to determine whether H(+)/K(+)-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H(+)/K(+)-ATPases are expressed in human pancreatic cells. Pumps have similar localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO(3) (-), pancreas also secretes K(+). In conclusion, this study calls for a revision of the basic model for HCO(3) (-) secretion. We propose that proton transport is driving secretion, and that in addition it may provide a protective pH buffer zone and K(+) recirculation. Furthermore, it seems relevant to re-evaluate whether PPIs should be used in treatment therapies where pancreatic functions are already compromised.
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spelling pubmed-44363732015-05-27 Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases Wang, Jing Barbuskaite, Dagne Tozzi, Marco Giannuzzo, Andrea Sørensen, Christiane E. Novak, Ivana PLoS One Research Article The mechanism by which pancreas secretes high HCO(3) (-) has not been fully resolved. This alkaline secretion, formed in pancreatic ducts, can be achieved by transporting HCO(3) (-) from serosa to mucosa or by moving H(+) in the opposite direction. The aim of the present study was to determine whether H(+)/K(+)-ATPases are expressed and functional in human pancreatic ducts and whether proton pump inhibitors (PPIs) have effect on those. Here we show that the gastric HKα1 and HKβ subunits (ATP4A; ATP4B) and non-gastric HKα2 subunits (ATP12A) of H(+)/K(+)-ATPases are expressed in human pancreatic cells. Pumps have similar localizations in duct cell monolayers (Capan-1) and human pancreas, and notably the gastric pumps are localized on the luminal membranes. In Capan-1 cells, PPIs inhibited recovery of intracellular pH from acidosis. Furthermore, in rats treated with PPIs, pancreatic secretion was inhibited but concentrations of major ions in secretion follow similar excretory curves in control and PPI treated animals. In addition to HCO(3) (-), pancreas also secretes K(+). In conclusion, this study calls for a revision of the basic model for HCO(3) (-) secretion. We propose that proton transport is driving secretion, and that in addition it may provide a protective pH buffer zone and K(+) recirculation. Furthermore, it seems relevant to re-evaluate whether PPIs should be used in treatment therapies where pancreatic functions are already compromised. Public Library of Science 2015-05-18 /pmc/articles/PMC4436373/ /pubmed/25993003 http://dx.doi.org/10.1371/journal.pone.0126432 Text en © 2015 Wang et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wang, Jing
Barbuskaite, Dagne
Tozzi, Marco
Giannuzzo, Andrea
Sørensen, Christiane E.
Novak, Ivana
Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title_full Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title_fullStr Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title_full_unstemmed Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title_short Proton Pump Inhibitors Inhibit Pancreatic Secretion: Role of Gastric and Non-Gastric H(+)/K(+)-ATPases
title_sort proton pump inhibitors inhibit pancreatic secretion: role of gastric and non-gastric h(+)/k(+)-atpases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436373/
https://www.ncbi.nlm.nih.gov/pubmed/25993003
http://dx.doi.org/10.1371/journal.pone.0126432
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