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.
Konturek
P C
PC
First Department of Medicine, University Erlangen-Nuernberg. Erlangen, Germany.
Konturek
S J
SJ
Hahn
E G
EG
D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D005744:Gastric Acid / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology*
D001639:Bicarbonates