THE ROLE OF CONSTITUTIVE AND INDUCIBLE NITRIC-OXIDE SYNTHASE IN SENNA-INDUCED AND CASCARA-INDUCED DIARRHEA IN THE RAT

The role of constitutive and inducible nitric oxide (NO) synthase in r ats treated with senna and cascara was studied. Senna (60 mg/kg p.o.) and cascara (800 mg/kg p.o.) ex vivo significantly increased Ca2+-depe ndent constitutive NO synthase activity in the rat colon. Induction of NO synthase (12% of the total NO synthase) was associated with cascar a, but not senna, administration. Dexamethasone (0.03-0.3 mg/kg i.p.), which inhibits the expression of inducible NO synthase, significantly and dose-dependently reduced cascara (but not senna-) induced diarrho ea and colonic fluid secretion. These findings suggest that senna prob ably exerts its laxative effect through stimulation of the constitutiv e isoform of NO synthase, while the inducible isoform of NO synthase a lso seems to be involved in the laxative effect of cascara. (C) 1997 E lsevier Science B.V.