Suppression of intestinal smooth muscle contraction by 4-ethylguaiacol, a constituent of wood creosote.
Wood creosote, a mixture of phenolic compounds, suppresses in vitro contractions of rat intestine. To identify a compound in wood creosote able to inhibit intestinal motility, we screened its constituent phenolic compounds and found 4-ethylguaiacol (4-EG) as an active compound. It suppressed the spontaneous phasic (IC50 = 513 +/- 48 mumol/l) as well as spasmogenic-agent-induced tonic longitudinal contractions of isolated rat ileum in a reversible and concentration-dependent manner. KCl-depolarization-induced tonic contraction, which was susceptible to a calcium channel blocking agent, was also suppressed by 4-EG with an IC50 of 433 +/- 41 mumol/l. Furthermore, calcium-ionophore-induced contraction, which was affected by an influx of extracellular calcium ion that bypassed calcium channels, was suppressed by 4-EG with an IC50 of 97 +/- 18 mumol/l. These results support the concept that the effect of wood creosote to suppress intestinal motility is attributable, partially or entirely, to its component 4-EG and that this effect of 4-EG on the intestinal muscle is produced at some stage(s) of the muscle contraction process after influx of extracellular calcium into the cytosol of smooth muscle.
Toyoda
M
M
Research Institute, Taiko Pharmaceutical Co., Ltd., Osaka, Japan.
Ogata
N
N
Shibata
T
T
D000818:Animals; D000930:Antidiarrheals / Q000032:analysis*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D003407:Creosote / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014934:Wood
D000930:Antidiarrheals; D015220:Calcium Channels; D011189:Potassium Chloride; D006139:Guaiacol; D003407:Creosote; C084991:4-ethylguaiacol; D002118:Calcium