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Inefficient chronic activation of parietal cells in Ae2a,b-/-
Authors: Recalde, S. (Sergio)
Burrell, M.A. (M.A.)
Martinez-Anso, E. (Eduardo)
Prieto, J. (Jesús)
Elferinh, R. (R.P.)
Saez, E. (Elena)
Kunne, C. (Cindy)
Looije, N. (Norbert)
Mardones, P. (Pablo)
Medina, J.F. (Juan Francisco)
Salas, J.T. (January T.)
Keywords: Gastrointestinal, Hepatobiliary and Pancreatic Pathology
Issue Date: 1-Jul-2006
Publisher: Elsevier
Publisher version: http://dx.doi.org/10.2353/ajpath.2006.051096
ISSN: 0002-9440
Citation: Recalde S, Muruzabal F, Looije N, Kunne C, Burrell MA, Saez E, et al. Inefficient chronic activation of parietal cells in Ae2a,b(-/-) mice. Am J Pathol 2006 Jul;169(1):165-176.
Abstract
In parietal cells, basolateral Ae2 C1 /HCO3 exchanger (S1c4a2) appears to compensate for luminal H pumping while providing C1 for apical secretion. In mouse and rat, mRNA variants Ae2a, Ae2b1, Ae2b2, and Ae2c2 are all found in most tissues (altough the latter at very low levels), whereas Ae2c1 is restricted to the stomach. We studied the acid secretory function of gastric mucosa in mice with targeted disruption of Ae2a, Ae2b1, and Ae2b2 (but not Ae2c) isoforms. In the oxyntic mucosa of Ae2a,b−/− mice, total Ae2 protein was nearly undetectable, indicating low gastric expression of the Ae2c isoforms. In Ae2a,b−/− mice basal acid secretion was normal, whereas carbachol/histamine-stimulated acid secretion was impaired by 70%. These animals showed increased serum gastrin levels and hyperplasia of G cells. Immunohistochemistry and electron microscopy revealed baseline activation of parietal cells with fusion of intracellular H+/K+-ATPase-containing vesicles with the apical membrane and degenerative changes (but not substantial apoptosis) in a subpopulation of these cells. Increased expression of proliferating cell nuclear antigen in the oxyntic glands suggested enhanced Ae2a,b−/− parietal cell turnover. These data reveal a critical role of Ae2a-Ae2b1-Ae2b2 isoforms in stimulated gastric acid secretion whereas residual Ae2c isoforms could account to a limited extent for basal acid secretion.
Permanent link: http://hdl.handle.net/10171/17303
Appears in Collections:DA - CIMA - Terapia génica y Hepatología - Anticuerpos monoclonales - Artículos de Revista
DA - Ciencias - HAP - Artículos de revista

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