Cysteamine-induced inhibition of acid neutralization and the increase in hydrogen ion back-diffusion in duodenal mucosa

Abstract

To investigate the possible impairment of defensive mechanisms in cysteamine-induced duodenal ulceration, the effect of cysteamine on the neutralization of acid by the duodenum and the back-diffusion of hydrogen ions into the duodenal mucosa has been studied. The results obtained were as follows. (1) The intraduodenal pH started to decrease between 3 and 4 hr after cysteamine injection. (2) By perfusion of the duodenal loop excluding the opening of bile and pancreatic ducts, the amount of hydrogen ions (H+) neutralized was found to be significantly lower in cysteamine-treated animals than in the controls. (3) the back-diffusion of luminal H+ into the duodenal mucosa, estimated by measuring the H+ disappearance from the test solution including 100 mM HCl, was significantly increased by cysteamine. From these findings, it has been concluded that cysteamine reduces the resistance of duodenal mucosa to acid coming from the stomach.

Specific Decrease in Alkaline Phosphatase Activity of Duodenal Mucosa in Rats Treated with Cysteamine

“…Therefore, it would not be unreasonable to speculate that oversecretion of gastric acid by the stomach may destroy the duodenal alkaline phosphatase activity, even though the pH of the intestinal luminal contents at the end of experiment was not lowered by cysteamine (Table 1). This view is supported by a previous observation that a transitory decrease of pH in the duodenal lumen was monitored by an impregnated pH microelectrode after cysteamine injection [19]. According to Garner et al [20], mucosal cells in the intestines are protected from acid by neutralization mechanisms of bicarbonate secretion and an unstirred water layer.…”

Augmentation of Cysteamine and Mepirizole-lnduced Lesions in the Rat Duodenum and Stomach by Histamine or Indomethacin

“…The damaged area of the histamine•cysteamine-induced duodenal lesions was about double that reported with indomethacin histamine-induced lesions (18 vs. 9.8 mm2) (7). Both mepirizole and cysteamine reduced duodenal HC03 secretion in rats in response to acid instillation, thereby resulting in a lowered acid neu tralization capacity (3,8,9). Therefore, the mechanism by which the combined adminis tration augments duodenal lesions appears to be an increase in aggressive factors in the stomach and a decrease in defensive factors both in the duodenum and stomach.…”

Histamine-induced villous damage in the rat duodenum.

“…It is most likely that the accumulation of gastric juice for longer periods might be caused by delayed gastric emptying. This accumulated gastric juice gradually empties into the duodenum which has an attenuated neutralizing capacity due to reduced HC03 secretion (4,12). The corrosive action of gastric acid on the duo denal mucosa results in villous damage, and finally, in penetrating ulcers.…”