Regulation of Smooth Muscle Contractility by the Epithelium in Rat Tracheas: Role of Prostaglandin E Induced by the Neurotransmitter Acetylcholine
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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.
Hiroshige T, Uemura K, Hirashima S, Togo A, Ohta K, Nakamura K Sci Rep. 2022; 12(1):9484.
PMID: 35676513 PMC: 9177838. DOI: 10.1038/s41598-022-13245-7.