A. Rubinstein et B. Tirosh, MUCUS GEL THICKNESS AND TURNOVER IN THE GASTROINTESTINAL-TRACT OF THERAT - RESPONSE TO CHOLINERGIC STIMULUS AND IMPLICATION FOR MUCOADHESION, Pharmaceutical research, 11(6), 1994, pp. 794-799
The thickness of the mucus gel and its turnover rate were measured in
the stomach, proximal jejunum, cecum and proximal colon of the rat, us
ing microscopy and staining techniques. The specific mucus-secretory r
esponses to carbachol-induced cholinergic stimulus in these locations
were also studied. The mucus gel was found to be the thinnest (18+/-1
microns) in the cecum, and the thickest in the stomach (39+/-14 micron
s). The effect of carbachol on mucus secretion was profound and dose d
ependent in the stomach, and less profound, although st:ll dose depend
ent, in the proximal jejunum. The least responsive organs were the cec
um and the proximal colon, where no effect was observed after three do
ses of carbachol. Mucus secretion rate was significantly higher in the
jejunum (1.1+/-0.5 mu g glucose equivalent min(-1) cm(-2)) than in th
e colon (0.5+/-0.2 pg glucose equivalent min(-1) cm(-2). Also, the pro
ximal jejunum was more responsive to the carbachol stimulus (mucus sec
retion rate of 5.4+/-2.2 mu g glucose equivalent min(-1) cm(-2) after
carbachol treatment) than the colon (mucus secretion rate of 1.0+/-0.4
mu g glucose equivalent min(-1) cm(-2) after carbachol treatment). In
vitro mucoadhesion studies with Polycarbophil disks were performed in
the mucosal tissues of the stomach, jejunum, cecum and proximal colon
of the rat with and without cholinergic (carbachol) stimulus. The adh
esion force in the cecum and the colon was significantly stronger than
in the stomach and proximal jejunum when the studies were performed a
t pH 2. Carbachol treatment did not significantly change the mucoadhes
ion of Polycarbophil disks. It is concluded that in the gastrointestin
al tract of the rat the colon and the cecum are more suitable location
s for the mucoadhesion than the stomach and the jejunum because: (1) t
heir mucus turnover is lower, (2) their sensitivity to mucus secretory
stimulus is lower, and (3) their Polycarbophil adherence properties a
re stronger.