Duodenal alkaline secretion: its mechanisms and role in mucosal protection against gastric acid

Duodenal mucosa, especially its proximal portion, is exposed to intermittent pulses of gastric acid (H+). This review summarises the mechanisms of duodenal bicarbonate (HCO3-) secretion and their role in protecting duodenal epithelium against gastric H+. Duodenal epithelium is a leaky barrier against gastric H+, which diffuses into duodenocytes, but fails to damage them due to: (a) an enhanced expression of cyclooxygenase, producing protective prostaglandins and expression of nitric oxide synthase, releasing nitric oxide, both stimulating duodenal HCO3- secretion and (b) the release of several neurotransmitters also stimulating HCO3- secretion such as vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, acetylcholine and melatonin. At the apical duodenocyte membrane, several HCO3-/Cl- anion exchangers operate in response to luminal H+ to extrude HCO3- into duodenal lumen. In baso-lateral duodenocyte membrane, both non-electrogenic and electrogenic Na+-HCO3- cotransporters are activated after exposure of duodenum to gastric H+, causing inward movement of HCO3- from extracellular fluid to duodenocytes. There are also at least three Na+/H+ exchangers, eliminating H+ which diffused into these cells. The Helicobacter pylori infection with gastric metaplasia in the duodenum and bacterium inoculation results in the inhibition of HCO3- secretion by its endogenous inhibitor dimethyl arginine, resulting in ulcerogenesis. (C) 2004 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.