Inhibition of rat intestinal Cl- secretion by 4,5-dimethylresorcinol

Wood creosote, a mixture of phenolic compounds, inhibits enterotoxin-induced intestinal fluid secretion, suggesting that one of its constituents suppresses transepithelial Cl- secretion from the intestinal mucosa. To identify an active constituent in wood creosote that inhibits intestinal Cl- secretion through Cl- channels, we first examined its effect on Cl- secretion using a cultured cell line transfected with complementary DNA encoding a Cl- channel and a Cl- -sensitive fluorescent dye. We next assayed chromatographic fractions of wood creosote for the inhibitory activity on Cl- secretion using a Ussing chamber. We found that 4,5-dimethylresorcinol, identified by gas chromatography-mass spectrometry, inhibited intestinal Cl- secretion dose-dependently when added to a serosal, but not mucosal, surface of rat jejunum, a half-inhibitory concentration being 3.8 microg/ml (28 micromol/l). It was strongly suggested that this effect was due to inhibition of Cl- channels.