Water extract of Helicobacter pylori inhibits duodenal mucosal alkaline secretion in anesthetized rats.
OBJECTIVE
The pathophysiology behind Helicobacter pylori-induced gastroduodenal dysfunction is incompletely understood. The aim of this study was to investigate if a water extract of H. pylori distorts acid-induced duodenal mucosal alkaline secretion.


METHODS
Chloralose-anesthetized rats were prepared for duodenal luminal perfusion and in situ pH-stat titration of mucosal alkaline secretion.


RESULTS
Mucosal bicarbonate secretion increased approximately 55%-60% after a 5-minute exposure to 10 mmol/L HCl. This response was absent when water extracts of three strains of H. pylori (protein content, 0.2-20 microg/mL) had been added to the perfusate. Presence of 3 mmol/L L-arginine, but not the stereoisomer D-arginine, in the luminal perfusate reversed the H. pylori extract blockade of acid-induced mucosal alkaline secretion. High-performance liquid chromatography-based analyses showed that the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) increased fourfold in duodenal perfusate and fivefold in duodenal tissue after H. pylori extract exposure. In vitro proteolysis of H. pylori extract also resulted in a substantial accumulation of ADMA. Exogenously administered ADMA, giving similar tissue concentrations, inhibited the mucosal alkaline response to acid exposure.


CONCLUSIONS
Water extracts of H. pylori inhibit acid-induced mucosal alkaline secretion via interference with mucosal NO synthase.
Fändriks
L
L
Department of Surgery, Göteborg University, Sweden.
von Bothmer
C
C
Johansson
B
B
Holm
M
M
Bölin
I
I
Pettersson
A
A
D000758:Anesthesia; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D004386:Duodenum / Q000378:metabolism*; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006851:Hydrochloric Acid / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006851:Hydrochloric Acid