Regulation of smooth muscle contractility by the epithelium in rat tracheas: role of prostaglandin E 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 level was measured using a Ca fluorescent probe Fluo-3 AM, and the fluorescence signal was recorded by a laser scanning confocal imaging system. The prostaglandin E (PGE) 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 showed a similar inhibitory effect on the EFS-evoked contraction of tracheal rings. Moreover, ACh triggered phospholipase C (PLC)-coupled Ca release from intracellular Ca stores and stimulated COX-dependent PGE production in primary cultured rat tracheal epithelial cells.

CONCLUSIONS

Collectively, this study demonstrated that ACh induced rat tracheal smooth muscle relaxation by promoting PGE release from tracheal epithelium, which might provide valuable insights into the cross-talk among neurons, epithelial cells and neighboring smooth muscle cells in airways.