Prostaglandin EP receptor subtypes and gastric cytoprotection

This article reviews recent studies dealing with the relationship between the cytoprotective action of PGE2 and the EP receptor subtypes in the gastric mucosa. Gastric cytoprotection afforded by PGE2 was mimicked by EP1 agonists and attenuated by the EP1 antagonist. Likewise, the adaptive cytoprotection induced by a mild irritant was attenuated by the EP1 antagonist and indomethacin. By contrast, capsaicin-induced protection was mitigated by indomethacin as well as sensory deafferentation but not by the EP1 antagonist. PGE2 failed to provide both direct and adaptive cytoprotection in EP1-receptor knockout mice, while capsaicin-induced protection was observed in the animals lacking either EP1 or EP3 receptors but disappeared in IP receptor knockout mice. We conclude that PGs, either generated endogenously or administered exogenously, exhibit gastric cytoprotection directly through activation of EP1 receptors, and endogenous PGs also contribute to the mucosal protection induced by capsaicin by sensitizing sensory neurons, probably through IP receptors.