STIMULATION BY MENTHOL OF CL SECRETION VIA A CA2+-DEPENDENT MECHANISM IN CANINE AIRWAY EPITHELIUM

1 To investigate the effect of menthol on airway epithelial ion transport function, we studied the bioelectrical properties of canine cultured tracheal epithelium by Ussing's short-circuit technique in vitro. 2 Addition of menthol (10(-3) M) to the mucosal but not the submucosal solution increased the short-circuit current (I-sc) from 6.2 +/- 0.9 to 14.0 +/- 2.2 mu A cm(-2) (P<0.001), and this effect was accompanied by increases in transepithelial potential difference and conductance. The response was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC(50)) being 6.4 +/- 0.9 mu A cm(-2) (P<0.001) and 40 mu M, respectively. 3 Other cyclic alcohols, including menthone and cyclohexanol, had no effect on the electrical properties. 4 The menthol-induced increase in I-sc was not altered by pretreatment of the cells with amiloride, indomethacin, or propranolol but was abolished by diphenylamine-2-carboxylate, furosemide or substitution of Cl with iodide in the medium. 5 Menthol (10(-3) M) increased cytosolic levels of free calcium ([Ca2+](i)) from 98 +/- 12 to 340 +/- 49 nM (P<0.01) in fura-2-loaded tracheal epithelium but did not affect the intracellular adenosine 3',5'-cyclic monophosphate content. 6 These results suggest that menthol stimulates Cl secretion across airway epithelium, probably through a Ca2+-dependent mechanism, and might thus influence mucociliary transport in the respiratory tract.