Role of PGE2/EP4 Receptor Signaling on The Effects of Hyperoxia on Airway Smooth Muscle

Abstract

It was shown that neonatal hyperoxic‐exposure associates with airway hyperresponsiveness and impaired nonadrenergic noncholinergic relaxation. It was demonstrated that reduced relaxant responses were associated with an impairment of prostaglandin E2 (PGE2) release from airway smooth muscle (ASM). In this study we tested the hypothesis that supplementation of PGE2 or EP4 agonists to ASM restore relaxant responses. Tracheal cylinders were obtained from 12 days rat pups exposed to hyperoxia or room air for seven days. These cylinders were used to study contractile and relaxant responses. In hyperoxic trachea the contractile responses to bethanechol were enhanced as compared to room air controls. These enhanced contractile responses were attenuated by pre‐incubation of tissues with PGE2 (1µM). Similar effect showed an EP4 agonist. This effect of PGE2 and EP4 agonist was reversed by an EP4 antagonist. PGE2 and EP4 induced dose response relaxations of ASM, which were reduced by an EP4 antagonist.We conclude that PGE2 induces relaxation of airways via EP4 receptors, and the use of EP4 agonists may serve as a therapeutic approach to overcome the adverse effects of neonatal hyperoxia on relaxant responses of ASM.Supported by MEST