Jun Tamaoki, Mitsuko Kondo, Atsushi Chiyotani, Hisashi Takemura and Kimio Konno
First Department of Medicine, Tokyo Women's Medical College, Tokyo 162, Japan
Abstract: The effect of Saiboku-to (TJ-96), an antiasthmatic Kampo medicine, on the generation of nitric oxide (NO) from cultured canine tracheal epithelium was investigated using a highly specific amperometric sensor for this molecule in vitro. Immersion of the NO-selective electrode in the medium containing tracheal epithelial cells detected the baseline current of 16.8-57.0 pA, which corresponded to an NO concentration ([NO]) of 39.7+-8.1 nM. Addition of TJ-96 increased [NO] in a concentration-dependent manner, the maximal increase from the baseline level and the concentration of TJ-96 required to produce a half-maximal effect (EC50) being 127.5+-20.1 nM (P<0.001) and 86+-9 microg/ml, respectively. Pretreatment of cells with NG-nitro-L-arginine methylester (L-NAME) greatly inhibited the TJ-96-induced increase in [NO], whereas NG-nitro-D-arginine methylester (D-NAME) had no effect, and this inhibition was reversed by L-arginine but not by D-arginine. Cytochemical staining of the epithelial cells showed marked reactivity of NADPH diaphorase activity. These results suggest that NO is spontaneously released by the airway epithelium and that TJ-96 stimulates the epithelial NO generation.
Keywords: Chinese medicine, Airway epithelium, Nitric oxide, Asthma