The inflammatory fluid secretion by the gallbladder mucosa in experimental
cholecystitis is induced by an activation of cyclooxygenase (COX), leading to an
increase in prostaglandin formation. This, in turn, activates intrinsic,
non-adrenergic non-cholinergic (NANC) secreto-motonerves to the mucosa (Jivegard
et al., Dig Dis Sci 1987;32;1389-1394). COX exists as a constitutive (COX-I),
and an inducible (COX-II) isoform. In the present study, we investigated a role
of COX-II for the inflammatory fluid secretion of the feline gallbladder.
Methods: Experiments were performed 10 weeks after a surgical procedure in
which chronic cholecystitis was induced in cats (n=11) by ligation of the cystic
duct and the implantation of (human) gallstones in the gallbladder. Six
previously unoperated animals served as controls. Gallbladder fluid transport
was continuously monitored via a perfusion system after the i.v. administration
of guanethidine and atropine.
Results: In inflamed gallbladders, there was steady fluid secretion that was
reversed to absorption by the i.v. injection of the selective COX-II blocker, NS
398. This agent did not affect the absorptive process of the gallbladder in the
controls. Increased levels of COX-II in inflamed, but not normal gallbladders
were shown by immunoblotting.
Transport of fluid (ml/h; mean ± SEM) in experiments
on cats with inflamed or normal gallbladder
Basal (ml/h) NS 398 (ml/h)
Inflamed gallbladders +0.28±0.07 -1.19±0.15***
Normal gallbladders -1.63±0.09 -1.61±0.10
***=p<0.001; ANOVA. + denotes secretion and - denotes absorption.
Conclusions: Increased levels of the inducible COX-II was shown in inflamed
gallbladders. Selective pharmacological blockade of COX-II abolished the
inflammatory fluid secretion. COX-II may be important in the regulation of the
gallbladder mucosal fluid transport in cholecystitis. Moreover, a COX-II
antagonist could be beneficial in human cholecystitis, with less side effects
compared to unselective blockers.
