Regulation of smooth muscle contractility by the epithelium in rat tracheas: role of prostaglandin E(2) induced by the neurotransmitter acetylcholine

BACKGROUND: Previous studies have suggested the involvement of epithelium in modulating the contractility of neighboring smooth muscle cells. However, the mechanism underlying epithelium-derived relaxation in airways remains largely unclear. This study aimed to investigate the mechanism underlying epithelium-dependent smooth muscle relaxation mediated by neurotransmitters. METHODS: The contractile tension of Sprague-Dawley (SD) rat tracheal rings were measured using a mechanical recording system. Intracellular Ca(2+) level was measured using a Ca(2+) fluorescent probe Fluo-3 AM, and the fluorescence signal was recorded by a laser scanning confocal imaging system. The prostaglandin E(2) (PGE(2)) content was measured using an enzyme-linked immunosorbent assay kit. RESULTS: We observed that the neurotransmitter acetylcholine (ACh) restrained the electric field stimulation (EFS)-induced contraction in the intact but not epithelium-denuded rat tracheal rings. After inhibiting the muscarinic ACh receptor (mAChR) or cyclooxygenase (COX), a critical enzyme in prostaglandin synthesis, the relaxant effect of ACh was attenuated. Exogenous PGE(2) showed a similar inhibitory effect on the EFS-evoked contraction of tracheal rings. Moreover, ACh triggered phospholipase C (PLC)-coupled Ca(2+) release from intracellular Ca(2+) stores and stimulated COX-dependent PGE(2) production in primary cultured rat tracheal epithelial cells. CONCLUSIONS: Collectively, this study demonstrated that ACh induced rat tracheal smooth muscle relaxation by promoting PGE(2) release from tracheal epithelium, which might provide valuable insights into the cross-talk among neurons, epithelial cells and neighboring smooth muscle cells in airways.