Glucocorticoids mediate reduction of epithelial acetylcholine content in the airways of rats and humans

The cholinergic system in rat and human airways and the effects of glucocorticoids were investigated by assay of choline acetyltransferase activity, by high-pressure liquid chromatography measurement of acetylcholine, and by anti-choline acetyltransferase immunocyto-/histochemistry. Human bronchi were obtained at surgery from patients with lung cancer. Group 1 patients did not suffer from additional lung diseases and had not been treated with glucocorticoids. Group 2 patients, who suffered in addition to lung cancer from chronic obstructive bronchitis, had been treated for at least 6 weeks before surgery with four puffs of flusinolid daily. Isolated bronchial epithelial cells as well as intact surface epithelium of human bronchi expressed choline acetyltransferase immunoreactivity and choline acetyltransferase enzyme activity (3 +/- 1 nmol/mg protein per h). Ciliated epithelial cells showed strong choline acetyltransferase immunoreactivity at the basal body and the roolet of cilia. Surface epithelium in group 1 and 2 bronchi contained 23 +/- 6 (n = 14) and 1.8 +/- 0.3 pmol/g acetylcholine) (n = 7, P < 0.001), respectively, whereas the transmural acetylcholine content did not differ significantly between both groups. The amount of choline acetyltransferase immunoreactivity appeared similar in the surface epithelium of both groups. In an animal (rat) study the effects of oral dexamethasone (3 mg/day, 1 week) on choline acetyltransferase activity and acetylcholine levels were investigated. Dexamethasone treatment reduced epithelial acetylcholine in the airways and small intestine by about 80% and inhibited epithelial choline acetyltransferase activity. In conclusion, epithelial cells of human airways possess components of the cholinergic system, i.e., contain the synthesizing enzyme choline acetyltransferase and store acetylcholine. The data obtained from the animal study indicate that glucocorticoids can inhibit epithelial acetylcholine. (C) 1998 Elsevier Science B.V. All rights reserved.