Prostaglandin and protection of the gastroduodenal mucosa

Abstract

The prostaglandins, PGs, are formed mainly from arachidonic acid by all nucleated cell populations in the human body. The biosynthesis is easily initiated by unspecific stimulation and is influenced by hormonal, neural and local factors. Human gastroduodenal tissue produces mainly PGE2 and PGF2; an atraumatic approach to follow local production is to identify luminal PGs and their metabolites. In the gastrointestinal tract, the most studied biological action of exogenous PGs is inhibition of the basal and stimulated gastric acid secretion. In addition, PGs stimulate the gastric and duodenal bicarbonate secretion and the production and release of mucus glycoproteins and may have trophic effects on the gastric mucosa. Thus, PGs seem capable of mobilizing all recognized mucosal defense factors. The ability of small amounts of orally administered PGs to protect the gastric mucosa against the gross damage produced by necrotizing agents in experimental animals and to prevent and heal gastroduodenal lesions in man is called "cytoprotection" and is independent of acid inhibition. Cytoprotection may be connected to stimulation of the defensive bicarbonate-mucus barrier or result from yet unidentified mechanisms. --Evidence suggesting a role for the locally biosynthesized PGs in the regulation of the gastric parietal and nonparietal secretions is indirect and based on studies with blocking of the PG-biosynthesis by antiphlogistic compounds. The possible importance of endogenous PGs in the pathophysiology of gastroduodenal disease has been insufficiently examined. --Analogues of PGE2, produced by total synthesis, combine acid antisecretory and cytoprotective properties at dose levels without side effects or systemic actions and are now being tested in clinical trials to confirm effectiveness in the prevention and treatment of peptic ulcer and other gastroduodenal lesions.