GLUCOCORTICOIDS MEDIATE REDUCTION OF EPITHELIAL ACETYLCHOLINE CONTENTIN THE AIRWAYS OF RATS AND HUMANS

The cholinergic system in rat and human airways and the effects of glu cocorticoids were investigated by assay of choline acetyltransferase a ctivity, by high-pressure liquid chromatography measurement of acetylc holine, and by anti-choline acetyltransferase immunocyto-/histochemist ry. Human bronchi were obtained at surgery from patients with lung can cer. Group 1 patients did not suffer from additional lung diseases and had not been treated with glucocorticoids. Group 2 patients, who suff ered in addition to lung cancer from chronic obstructive bronchitis, h ad been treated for at least 6 weeks before surgery with four puffs of flusinolid daily. Isolated bronchial epithelial cells as well as inta ct surface epithelium of human bronchi expressed choline acetyltransfe rase 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 ac etyltransferase immunoreactivity appeared similar in the surface epith elium of both groups. In an animal (rat) study the effects of oral dex amethasone (3 mg/day, 1 week) on choline acetyltransferase activity an d acetylcholine levels were investigated. Dexamethasone treatment redu ced epithelial acetylcholine in the airways and small intestine by abo ut 80% and inhibited epithelial choline acetyltransferase activity. In conclusion, epithelial cells of human airways possess components of t he cholinergic system, i.e., contain the synthesizing enzyme choline a cetyltransferase and store acetylcholine. The data obtained from the a nimal study indicate that glucocorticoids can inhibit epithelial acety lcholine. (C) 1998 Elsevier Science B.V. All rights reserved.