Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

STOMACH SECRETORY FUNCTION UNDER MUSCLE LOAD IN THE CONDITIONS OF PHARMACOLOGICAL BLOCADE OF M-CHOLINORECEPTORS AND β-ADRENOCEPTORS

Aim. The article deals with establishing the effect of muscle load on the stomach secretory function in the conditions of partial pharmacological blockade of M-cholinoreceptors and β-adrenoceptors in patients with duodenal acidification. Materials and methods. 22 males aged 18–23 years participated in the study. The stomach secretory function at rest under a 30-minute cycle ergometer load of 36 900 kgm combined with a partial pharmacological blockade of M-cholinoreceptors (1.5 mg per kg of body mass) and β-adrenoceptors (0.6 mg obsidan per kg of body mass) was studied using gastric and gastroduodenal intubation. Results. The blockade of M-cholinoreceptors at muscle rest provoked a noticeable decrease in the total content of electrolytes (p < 0.01), enzymes (p < 0.001), HCL (p < 0.001), and proteolytic activity (p < 0.001) in gastric juice. The combined activity of atropine and physical load in the conditions of duodenal acidification inhibited the amount of secretion significantly to 49.9 ± 11.1%, HCl to 29.7 ± 9.4%, pepsinogen to 19.8 ± 7.4% (p ˂ 0.001). The blockade of β-adrenoceptors significantly decreased the stomach secretory function in the conditions of basal secretion and duodenal acidification. After using a 10% dried cabbage decoction as a stimulator we registered an increase in the amount of secretion up to 141.1 ± 12.2%, HCl discharge – to 186.3 ± 21.9%, and pepsinogen – to 188.5 ± 20.4%. The same tendency was registered for the cycle ergometer test in the conditions of the blockade of β-adrenoceptors. Conclusion. The effect of muscle load on the stomach secretory function contributes significantly to the role of the sympathetic nervous system. Duodenal acidification in the conditions of the blockade of β-adrenoceptors intensifies the inhibitory effect, while stimulation with a dry cabbage decoction improves the stomach secretory function.

Influence of duodenal acidification on the sensorimotor function of the proximal stomach in humans

Decreased acid clearance and increased exposure to acid of the duodenum have been reported in a subset of functional dyspepsia patients. However, the mechanism by which increased duodenal acid exposure may affect symptoms is unclear. The aim of the present study was to investigate the effects of duodenal acidification on proximal gastric tone and mechanosensitivity in humans. An infusion tube with a pH electrode attached was positioned in the second part of the duodenum, and a barostat bag was located in the gastric fundus. In 12 healthy subjects, fundic tone and sensitivity to distensions were assessed before and during duodenal infusion of 0.1 N hydrochloric acid or saline in a randomized, double-blind design. In 10 healthy subjects, meal-induced accommodation was measured during duodenal infusion of acid or saline. Acid infusion in the duodenum significantly increased fundic compliance and decreased fasting fundic tone. This was accompanied by a significant decrease in the pressures and the corresponding wall tensions at the thresholds for discomfort. During infusion of acid, significantly higher perception and symptom scores were obtained for the same distending pressures. The meal-induced fundic relaxation was significantly smaller during acid infusion compared with saline infusion. In conclusion, duodenal acidification induces proximal gastric relaxation, increases sensitivity to gastric distension, and inhibits gastric accommodation to a meal. Through these mechanisms, increased duodenal acid exposure may be involved in the pathogenesis of dyspeptic symptoms.