Besides their broad distribution in the nervous system, nicotinic acetylcholine receptors are also widely distributed in non-neuronal tissues. Thus there have been different subunits of nicotinic receptors as well as further components of the cholinergic system detected for example in epithelial cells of the respiratory tract. The non-neuronal impact of acetylcholine (ACh) on the tracheal epithelium is so far not investigated in detail.

The aim of this study was to characterize the influence of nicotine on the ion-transport in the tracheal epithelium of the mouse considering a putative relevance of nicotinic ACh receptors as signaling mediators. To achieve this aim, the impact of nicotine on freshly isolated mouse tracheas (C57/Bl6) was analyzed with electrophysiological experiments by using the Ussing-chamber-technique. In these measurements the transepithelial short circuit current (I_sc) was recorded. For further characterization of the nicotinic effect different modulators of nicotinic receptors and ion-channels have been used. Apical application of nicotine (100 mM) led to a transient increase of the Isc that could be inhibited completely by mecamylamine, a general inhibitor of nicotinic receptors. In contrast to this finding the antagonist of a 7/9/10-subunits methyllycaconitine (MLA), could not abolish the impact of nicotine although the effect was attenuated compared to control conditions. This indicates, that the effect is probably mainly mediated by nicotinic receptors that are assembled of heteromeric a- and ß-subunits. A contribution of the epithelial sodium channel to the nicotine-induced increase of the current could be excluded by investigations with amiloride. The effect of nicotine was inhibited by apical perfusion with blockers of chloride channels (NPPB and NFA). Thus, binding of a ligand to the nicotinic receptors obviously evokes an activation of apical chloride conductances.

Taken together these data indicate that functional nicotinic ACh receptors exist in the tracheal epithelium of the mouse and that these receptors induce an apical chloride secretion. This indicates a contribution of the nicotinic receptors to transepithelial ion transport and thus to the regulation of the mucociliary clearance.