Proliferative effect of acetylcholine on rat trachea epithelial cells is mediated by nicotinic receptors and muscarinic receptors of the M1-subtype

Acetylcholine (ACh), synthesized in mammalian non-neuronal cells such as epithelial cells of the airways, digestive tract and skin, is involved in the regulation of basic cell functions (so-called non-neuronal cholinergic system). In the present experiments rat trachea epithelial cells have been cultured to study the proliferative effect of applied ACh by [H-3]thymidine incorporation. ACh (exposure time 24 h) caused a concentration-dependent increase in cell proliferation with a doubling of the [H-3]thymidine incorporation at a concentration of 0.1 muM. This effect was partly reduced by 30 muM tubocurarine and completely abolished by the additional application of 1 muM atropine. The stimulatory effect of acetylcholine, remaining in the presence of tubocurarine, was prevented by 1 muM pirenzepine (preferentially acting at M1-receptors), but neither by 1 muM AFDX 116 (preferentially acting at M-2-receptors) nor by 1 muM hexahydrosiladifenidol (preferentially acting at M3-receptors). The combination of tubocurarine and pirenzepine halved the basal [H-3]thymidine incorporation. In conclusion, ACh produces a proliferative effect in rat trachea epithelial cells, the effect being mediated by both nicotinic receptors and muscarinic receptors of the M1-subtype. (C) 2003 Elsevier Science Inc. All rights reserved.