title: Stimulation by menthol of Cl secretion via a Ca(2+)-dependent mechanism in canine airway epithelium.
abstract: 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 (Isc) from 6.2 +/- 0.9 to 14.0 +/- 2.2 microA 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 (EC50) being 6.4 +/- 0.9 microA cm-2 (P < 0.001) and 40 microM, respectively. 3. Other cyclic alcohols, including menthone and cyclohexanol, had no effect on the electrical properties. 4. The menthol-induced increase in Isc 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 Ca(2+)-dependent mechanism, and might thus influence mucociliary transport in the respiratory tract.
authors.affiliation: First Department of Medicine, Tokyo Women's Medical College, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Chiyotani
authors.forename: J
authors.initials: J
authors.lastname: Tamaoki
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: K
authors.initials: K
authors.lastname: Isono
authors.forename: K
authors.initials: K
authors.lastname: Konno
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D004594:Electrophysiology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005260:Female; D016257:Fura-2; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008610:Menthol / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002712:Chlorides; D008610:Menthol; D000242:Cyclic AMP; D002118:Calcium; D016257:Fura-2; D007213:Indomethacin