Stimulation by menthol of Cl secretion via a Ca(2+)-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 incr...

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Bibliographic Details
Published in:British journal of pharmacology 1994-06, Vol.112 (2), p.571-575
Main Authors: Chiyotani, A, Tamaoki, J, Takeuchi, S, Kondo, M, Isono, K, Konno, K
Format: Article
Language:English
Subjects:
Animals
Calcium - metabolism
Calcium - physiology
Cells, Cultured
Chlorides - metabolism
Cyclic AMP - metabolism
Cytosol - metabolism
Dogs
Electrophysiology
Epithelium - drug effects
Epithelium - metabolism
Female
Fura-2
In Vitro Techniques
Indomethacin - pharmacology
Male
Menthol - pharmacology
Stimulation, Chemical
Trachea - drug effects
Trachea - metabolism
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Summary: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.
ISSN:0007-1188
DOI:10.1111/j.1476-5381.1994.tb13112.x