It has been documented that topical administration of lidocaine can cause airway complications, although it is the most used local anesthetic for laryngotracheal anesthesia. Thus, in this study we investigated the local actions of lidocaine on basal and autonomic secretagogue-induced ion transport in cultured swine tracheal submucosal gland cells. Ion transport plays an important role in maintaining effective mucociliary clearance and pulmonary defense mechanisms. It was measured as short-circuit current (Isc) utilizing Ussing chamber methodology. Exposure of cultured gland cells to lidocaine evoked a transient response with an initial increase in Isc followed by a decrease. The increase in Isc induced by lidocaine (3 mM) was 8.0 +/- 1.5 microA/cm(2). The maximal increases in Isc induced by isoproterenol and acetylcholine were 9.4 +/- 0.6 and 38.3 +/- 2.3 microA/cm(2), respectively. However, lidocaine significantly decreased the isoproterenol-induced increases in Isc. Acetylcholine-induced responses were not changed by lidocaine. Atropine did not significantly affect lidocaine-evoked events in ion transport. These results suggest that lidocaine directly alters epithelial transport of ions and also inhibits the adrenergic stimulation of epithelial ion transport. Copyright 2000 Academic Press.