M. Toyoda et al., SUPPRESSION OF INTESTINAL SMOOTH-MUSCLE CONTRACTION BY 4-ETHYLGUAIACOL, A CONSTITUENT OF WOOD CREOSOTE, Pharmacology, 47(5), 1993, pp. 300-308
Wood creosote, a mixture of phenolic compounds, suppresses in vitro co
ntractions of rat intestine. To identify a compound in wood creosote a
ble to inhibit intestinal motility, we screened its constituent phenol
ic compounds and found 4-ethylguaiacol (4-EG) as an active compound. I
t suppressed the spontaneous phasic (IC50 = 513 +/- 48 mumol/l) as wel
l as spasmogenic-agent-induced tonic longitudinal contractions of isol
ated 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 IC
50 of 433 +/- 41 mumol/l. Furthermore, calcium-ionophore-induced contr
action, which was affected by an influx of extracellular calcium ion t
hat bypassed calcium channels, was suppressed by 4-EG with an IC50 of
97 +/- 18 mumol/l. These results support the concept that the effect o
f wood creosote to suppress intestinal motility is attributable, parti
ally or entirely, to its component 4-EG and that this effect of 4-EG o
n the intestinal muscle is produced at some stage(s) of the muscle con
traction process after influx of extracellular calcium into the cytoso
l of smooth muscle.