Distribution of Prostaglandin E2 in Gastric and Duodenal Mucosa: Possible Role in the Pathogenesis of Peptic Ulcer

Abstract

BackgroundProstaglandin E which is present abundantly in the gastric mucosa is a powerful inhibitor of gastric acid secretion and a stimulus to gastric mucus production. In addition, prostaglandin E2 inhibits ulcer formation in animals, and the synthetic analogues of prostaglandin E have successfully been used in the treatment of patients with gastric and duodenal ulcer disease. To evaluate the role of endogenous prostaglandin E2 in the pathogenesis of the peptic ulcer disease, we measured mucosal prostaglandin E2 levels in patients with gastric and duodenal ulcer disease and compared with that of non-ulcer control persons.MethodsThe study population was made up of 44 non-ulcer persons, 36 patients with a benign gastric ulcer, and 48 with a duodenal ulcer. Every mucosai specimen, taken from the antrum and from the duodenal bulb, were homogenized, mixed with 1 M HCI, and centrifuged. After removal of the supernatant, precipitate was eluted with ethyl acetate in the Amprep C18 minicolumn. Then the extracted prostaglandin E2 in the ethyl acetate fractions was converted into its methyl oximate derivatives, and the prostaglandin E2 level was measured by radioimmunoassay. During the procedure any homogenized specimen which was looking grossly bloody was removed from the assay in order to avoid any possible contamination or prostaglandin E2 in blood.ResultsIn non-ulcer persons, the mean values was 258.17±127.03 pg/mg. tissue in antrum and 121.07±67.46 pg/mg. tissue in duodenal bulb. The corresponding values were 186.42±70.51 pg/mg. tissue, 79.44±39.04 pg/mg. tissue in gastric ulcer patients and 204. 94 92.03 pg/mg. tissue, 99.66±56.10 pg/mgl. tissue in duodenal ulcer patients respectively. Gastric ulcer patients have the significantly lower level of the antral and duodenal prostaglandin E2 (p<0.005). Those levels of duodenal ulcer patients were also significantly lower than those of non-ulcer persons (p<0.025 & 0.05). Antral prostaglandin E2 level increased to 305.21±104.91 pg/mg. tissue in the gastric ulcer patients (p<0.005) and to 271.02±93.23 pg/mg. tissue in the duodenal ulcer (p<0.005) when the ulcer crater was healed. The duodenal bulb prostaglandin E2 level was also increased in the healed stage of ulcer, e. g., 128.84±57.62 (p<0.005) and 112.60±42.25 pg/mg. tissue, respectively.ConclusionThese results suggest that prostaglandin deficiency in the antral and duodenal bulb mucosa may have an important role in the pathogenesis of peptic ulcer disease.

Oestrogen upregulates the expression levels and functional activities of duodenal mucosal CFTR and SLC26A6

“…We found that basal and both forskolin-and PGE 2 -stimulated duodenal mucosal bicarbonate secretion was markedly diminished in ovariectomized mice. In humans, PGE 2 was a major product produced by the duodenal mucosa (Konturek et al 1981;Hillier et al 1985;Aly et al 1987;Park et al 1992). The results demonstrate that oestrogen upregulates the functional activities of CFTR and SLC26A6, which contributes to explaining the sex difference in duodenal mucosal bicarbonate secretion.…”

“…In various species, gastric and duodenal mucosae were found to be capable of generating large mounts of PGE 2 (Ahlquist et al 1982;Aly et al 1987;Kapicioglu et al 1990). In humans, PGE 2 was a major product produced by the duodenal mucosa (Konturek et al 1981;Hillier et al 1985;Aly et al 1987;Park et al 1992). In physiological conditions, gastric acid is an important stimulant of proximal duodenal mucosal bicarbonate secretion (Allen & Flemström, 2004;Konturek et al 2004), and studies have demonstrated that endogenous PGE 2 is the most important intramucosal mediator of gastric acid-stimulated duodenal bicarbonate secretion (Bukhave et al 1990;Takeuchi et al 1999;Sugamoto et al 2001).…”