Regulation of smooth muscle contractility by the epithelium in rat tracheas: role of prostaglandin E₂ induced by the neurotransmitter acetylcholine.

ABSTRACT:

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 Ca²⁺ level was measured using a Ca²⁺ fluorescent probe Fluo-3 AM, and the fluorescence signal was recorded by a laser scanning confocal imaging system. The prostaglandin E₂ (PGE₂) 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 PGE₂ showed a similar inhibitory effect on the EFS-evoked contraction of tracheal rings. Moreover, ACh triggered phospholipase C (PLC)-coupled Ca²⁺ release from intracellular Ca²⁺ stores and stimulated COX-dependent PGE₂ production in primary cultured rat tracheal epithelial cells.

Conclusions

Collectively, this study demonstrated that ACh induced rat tracheal smooth muscle relaxation by promoting PGE₂ release from tracheal epithelium, which might provide valuable insights into the cross-talk among neurons, epithelial cells and neighboring smooth muscle cells in airways.

SUBMITTER: Zhao L 

PROVIDER: S-EPMC7944331 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature