Gastrointestinal cytoprotection by prostaglandin E and EP receptor subtypes

Abstract

Endogenous prostaglandins (PGs) play important roles in modulating the mucosal integrity and various functions of the gastrointestinal tract. Among them, E-type PGs are most effective in these actions. This article reviews recent studies dealing with the relationship of the cytoprotective action of PGE2- and EP-receptor subtypes in the gastrointestinal mucosa. PGE2 exerts gastric cytoprotection against HC1/ethanol and indomethacin. These effects were mimicked by only EP1 agonists and attenuated by EP1 antagonists. Likewise, the adaptive cytoprotection induced by a mild irritant was attenuated by EP1 antagonists as well as indomethacin. On the other hand, the protective effect of dmPGE2 against indomethacin-induced small intestinal lesions was mimicked by only EP3 and EP4 agonists. Similar results were obtained in EP-receptor knockout mice; ie., PGE2 failed to exhibit both direct and adaptive cytoprotection in EP1-receptor knockout mice, while the protective action in both the duodenum and small intestine was hampered in EP3-receptor knockout mice. The underlying mechanism related to these actions of PGE2 in the stomach, duodenum or small intestine may be related to inhibition of stomach contraction, stimulation of duodenal alkaline secretion, or suppression of bacterial translocation due to inhibition of intestinal contraction as well as stimulation of mucus secretion, respectively.