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.
Ogata
Norio
N
Taiko Pharmaceutical Co, Ltd, Osaka, Japan. ogata@r9.dion.ne.jp
Shibata
Takashi
T
D000818:Animals; D045744:Cell Line, Tumor; D002712:Chlorides / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003407:Creosote / Q000737:chemistry; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012118:Resorcinols / Q000494:pharmacology*
C505032:CFTR protein, human; D002712:Chlorides; D005456:Fluorescent Dyes; D007473:Ion Channels; D012118:Resorcinols; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C010609:4-methylorcinol; D003407:Creosote