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Am J Physiol Cell Physiol 288: C1-C19, 2005; doi:10.1152/ajpcell.00102.2004
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INVITED REVIEW

Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin

Adrian Allen1 and Gunnar Flemström2

1Physiological Sciences, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; and 2Division of Physiology, Department of Neuroscience, Uppsala University, Uppsala, Sweden

Secretion of bicarbonate into the adherent layer of mucus gel creates a pH gradient with a near-neutral pH at the epithelial surfaces in stomach and duodenum, providing the first line of mucosal protection against luminal acid. The continuous adherent mucus layer is also a barrier to luminal pepsin, thereby protecting the underlying mucosa from proteolytic digestion. In this article we review the present state of the gastroduodenal mucus bicarbonate barrier two decades after the first supporting experimental evidence appeared. The primary function of the adherent mucus gel layer is a structural one to create a stable, unstirred layer to support surface neutralization of acid and act as a protective physical barrier against luminal pepsin. Therefore, the emphasis on mucus in this review is on the form and role of the adherent mucus gel layer. The primary function of the mucosal bicarbonate secretion is to neutralize acid diffusing into the mucus gel layer and to be quantitatively sufficient to maintain a near-neutral pH at the mucus-mucosal surface interface. The emphasis on mucosal bicarbonate in this review is on the mechanisms and control of its secretion and the establishment of a surface pH gradient. Evidence suggests that under normal physiological conditions, the mucus bicarbonate barrier is sufficient for protection of the gastric mucosa against acid and pepsin and is even more so for the duodenum.

acid-base transporters; cystic fibrosis transmembrane conductance regulator channel; surface pH gradient; mucus gels; trefoil peptides



Address for reprint requests and other correspondence: G. Flemström, Division of Physiology, Dept. of Neuroscience, Uppsala Univ., BMC, PO Box 572, SE-751 23 Uppsala, Sweden (E-mail: Gunnar.Flemstrom{at}Fysiologi.uu.se)




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