Ek. O'Donnell et al., Inhibition of enterotoxin-induced porcine colonic secretion by diarylsulfonylureas in vitro, AM J P-GAST, 279(5), 2000, pp. G1104-G1112
Citations number
38
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Muscle-stripped piglet colon was used to evaluate changes in short-circuit
current (I-sc) as an indicator of anion secretion. Mucosal exposure to Esch
erichia coli heat-stable (STa) or heat-labile enterotoxins (LT) stimulated
I-sc by 32 +/- 5 and 42 +/- 7 muA/cm(2), respectively. Enterotoxin-stimulat
ed I-sc was not significantly affected by either 4,4'-diaminostilbene- 2,2'
-disulfonic acid or CdCl2, inhibitors of Ca2+-activated Cl- channels and Cl
C-2 channels, respectively. Alternatively, N-(4-methylphenylsulfonyl)-N'-(4
-trifluoromethylphenyl) urea (DASU-02), a compound that inhibits cystic fib
rosis transmembrane conductance regulator (CFTR)-mediated Cl- secretion, re
duced I-sc by 29 +/- 7 and 34 +/- 11 mA/cm(2), respectively. Two additional
diarylsulfonylurea (DASU) based compounds were evaluated for their effects
on enterotoxin-stimulated secretion. The rank order of potency for inhibit
ion by these three closely related DASU structures was identical to that ob
served for human CFTR. The degree of inhibition by each of these compounds
was similar for both STa and LT. The structure- and concentration-dependent
inhibition shown indicates that CFTR mediates both STa- and LT-stimulated
colonic secretion. Similar structure- dependent inhibitory effects were obs
erved in forskolin-stimulated rat colonic epithelium. Thus DASUs compose a
family of inhibitors that may be of therapeutic value for the symptomatic t
reatment of diarrhea resulting from a broad spectrum of causative agents ac
ross species.