Stimulation of Na absorption by the antiasthmatic kampo drug Saiboku-to in cultured airway epithelium.
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 microA/cm2 (P less than 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 less than 0.001) and 3 micrograms/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.
Tamaoki
J
J
First Department of Medicine, Tokyo Women's Medical College, Japan.
Takeyama
K
K
Chiyotani
A
A
Sakai
N
N
Takizawa
T
T
Konno
K
K
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D008297:Male; D020835:Medicine, Kampo; D011199:Potentiometry; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*; D014132:Trachea / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D006634:Histamine H1 Antagonists; C045086:saiboku-to; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase