Barnett K, Jacoby D B, Nadel J A, Lazarus S C
Cardiovascular Research Institute, University of California, San Francisco 94143.
Am Rev Respir Dis. 1988 Oct;138(4):780-3. doi: 10.1164/ajrccm/138.4.780.
Airway epithelial cells produce mediators that play a role in regulating airway smooth muscle function. This study was designed to examine the effects of epithelial-derived products on contraction of airway smooth muscle. To avoid biochemical and physical changes that may be produced by stripping epithelium from tracheal smooth muscle, we examined the effect of products from pure cultured tracheal epithelial cells on intact dog tracheal smooth muscle. When bradykinin (10(-5) M) was added to dog epithelial cells in culture and the supernatant was added to strips of isolated tracheal smooth muscle, contractile responses to electrical field stimulation were significantly inhibited. Pretreatment of the epithelial cells with indomethacin (5.6 x 10(-6) M) inhibited this effect. Bradykinin placed directly on the canine smooth muscle had no effect on resting tension or on the response to electrical field stimulation. Contractions of the smooth muscle to exogenous acetylcholine were unaffected by supernatants from either indomethacin-treated or untreated cells stimulated with bradykinin (10(-5) M) compared to time controls. We conclude that bradykinin stimulates the release of a cyclooxygenase-dependent inhibitory factor from airway epithelial cells. This factor is likely to be prostaglandin E2, which is generated by the epithelial cells in response to bradykinin stimulation and inhibits smooth muscle contraction induced by electrical field stimulation. Although the mechanism of this inhibition is unknown, the normal response to exogenous acetylcholine is consistent with the hypothesis that prostaglandin E2 acts by inhibiting cholinergic neurotransmitter release at a prejunctional site.
气道上皮细胞产生的介质在调节气道平滑肌功能中发挥作用。本研究旨在探讨上皮来源产物对气道平滑肌收缩的影响。为避免因从气管平滑肌剥离上皮而可能产生的生化和物理变化，我们研究了纯培养的气管上皮细胞产物对完整犬气管平滑肌的影响。当将缓激肽（10⁻⁵ M）加入培养的犬上皮细胞中，并将上清液加入分离的气管平滑肌条时，对电场刺激的收缩反应明显受到抑制。用吲哚美辛（5.6×10⁻⁶ M）预处理上皮细胞可抑制这种作用。将缓激肽直接作用于犬平滑肌对静息张力或对电场刺激的反应没有影响。与时间对照相比，用缓激肽（10⁻⁵ M）刺激的吲哚美辛处理或未处理细胞的上清液对平滑肌对外源性乙酰胆碱的收缩没有影响。我们得出结论，缓激肽刺激气道上皮细胞释放一种依赖环氧化酶的抑制因子。该因子可能是前列腺素E2，它由上皮细胞在缓激肽刺激下产生，并抑制电场刺激诱导的平滑肌收缩。尽管这种抑制机制尚不清楚，但对外源性乙酰胆碱的正常反应与前列腺素E2通过抑制节前部位胆碱能神经递质释放起作用的假设一致。
