Serotonin (10(-6)-10(-4) M) produced relaxations in a concentration-de
pendent (at 10(-6) and 10(-5) M concentrations) manner followed by a c
ontraction (at 10(-4) M concentration) in a co-axial system, which con
sisted of guinea-pig trachea as a donor organ for epithelial derived-r
elaxing factor(s) and phenylephrine-precontracted rat anococcygeus mus
cle as assay tissue. Serotonin produced a concentration-dependent cont
raction only in precontracted rat anococcygeus muscle mounted alone or
mounted co-axially within epithelium-denuded trachea. Indomethacin (1
0(-6) M) significantly inhibited the initial relaxations (from 25.1 +/
- 7.8 to 7.8 +/- 5.0% and from 35.6 +/- 8.7 to 10.4 +/- 8.3% at 10(-6)
and 10(-5) M concentrations of serotonin), but did not affect the con
traction. Imipramine (10(-8) M) and hydrocortisone (3 X 10(-5) M) redu
ced the initial relaxations (from 20.5 +/- 1.6 to 3.8 +/- 1.5% and fro
m 32.1 +/- 6.4 to 18.9 +/- 3.9% at 10(-6) M and 10(-5) M concentration
s of serotonin, respectively) and also converted the serotonin (10(-4)
M)-induced contraction to a relaxation. In the co-axial system with t
rachea from guinea-pigs previously sensitized with i.p. injected egg-o
valbumin, the serotonin-induced biphasic response was converted to a c
ontractile response only after ovalbumin challenge. Histopathologic ch
anges were observed in the epithelium of challenged tracheas taken fro
m sensitized guinea-pigs and alterations of serotonin-induced epitheli
um-dependent responses were attributed to the morphological and/or fun
ctional damage of tracheal epithelium caused by ovalbumin challenge. I
n the modified co-axial system, phenylephrine-induced contractions fad
ed quickly when the rat anococcygeus muscle was mounted in epithelium-
intact guinea-pig trachea, and the percentage fade was significantly h
igher (92.3 +/- 2.8%) than that obtained when the anococcygeus muscle
was mounted in epithelium-denuded trachea (56.9 +/- 8.4%) or when it w
as mounted alone (44.6 +/- 7.7%). Our results suggest that guinea-pig
tracheal epithelium is capable of modulating the responsiveness of rat
anococcygeus muscle to serotonin by affecting the basal or stimulated
release of some inhibitory mediators.