Duodenal mucosal protection by bicarbonate secretion and its mechanisms.
Proximal portion of duodenum is exposed to intermittent pulses of gastric H(+) discharged by the stomach. This review summarizes the mechanisms of duodenal mucosal integrity, mainly the role of mucus-alkaline secretion and the mucous barrier protecting surface epithelium against gastric H(+). The mucous barrier protects the leaky duodenal epithelium against each pulse of gastric H(+), which penetrates this barrier and diffuses into duodenocytes, but fails to damage them due to; a) an enhanced expression of cyclooxygenase-1 (COX-1), with release of protective prostaglandins (PG) and of nitric oxide (NO) synthase (NOS) with, however, production of NO, stimulating duodenal HCO(3)(-) secretion and b) the release of several neurotransmitters also stimulating HCO(3)(-) secretion such as vasoactive intestinal peptide (VIP), pituitary adenylate-cyclase activating polypeptide (PACAP), acetylcholine, melatonin, leptin and ghrelin released by enteric nerves and mucosal cells. At the apical duodenocyte membrane at least two HCO(3)(-)/Cl(-) anion exchangers operate in response to luminal H(+) to provide adequate extrusion of HCO(3)(-) into duodenal lumen. In the basolateral portion of duodenocyte membrane, both non-electrogenic (NBC) and electrogenic (NBC(n)) Na(+) HCO(3)(-) cotransporters are activated by the exposure to duodenal acidification, causing inward movement of HCO(3)(-) from extracellular fluid to duodenocytes. There are also at least three Na(+)/H(+) (NHE1-3) amiloride-sensitive exchangers, eliminating H(+)which diffused into these cells. The Helicobacter pylori (Hp) infection and gastric metaplasia in the duodenum with bacterium inoculating metaplastic mucosa and inhibiting HCO(3)(-) secretion by its endogenous inhibitor, asymmetric dimethyl arginine (ADMA), may result in duodenal ulcerogenesis.
Konturek
S J
SJ
Department of Physiology, Jagiellonian University Medical College, Cracow, Poland. mpkontur@cyf-kr.edu.pl
Konturek
P C
PC
Pawlik
T
T
Sliwowski
Z
Z
Ochmański
W
W
Hahn
E G
EG
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism* / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D005744:Gastric Acid / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*
D001639:Bicarbonates