Stimulation of Na Absorption by the Antiasthmatic Kampo Drug Saiboku-to in Cultured Airway Epithelium

Abstract

To study the effect of the Kampo drug Saiboku-to (TJ-96) on ion transport function of airway epithelial cells, we studied bioelectric properties of cultured tracheal epithelium from dogs under short-circuit conditions in vitro. Addition of TJ-96 (1 mg/ml) to the mucosal solution of the Ussing chamber increased the epithelial short-circuit current (SCC) from 6.5 ± 0.7 to 11.4 ± 1.6 µA/cm2 (P < 0.001). This effect was dose-dependent, with the maximal increase from the baseline value and the concentration required to produce a half-maximal effect (EC50) being 70.5 ± 12.6% (P < 0.001) and 3 µgrams/ml, respectively; and there were corresponding increases in transepithelial potential difference and cell conductance. Submucosal addition of TJ-96 likewise increased SCC, although the magnitude of the response was smaller as compared with the response to the mucosal addition. The TJ-96-induced increase in SCC was not affected by diphenylamine-2-carboxylate or furosemide but abolished by amiloride. Intracellular cyclic AMP levels were dose-dependently increased by TJ-96. These results indicate that TJ-96 may selectively stimulate Na absorption across the tracheal epithelium, probably through intracellular accumulation of cyclic AMP.