EFFECT OF COLCHICINE AND BISACODYL ON RAT INTESTINAL TRANSIT AND NITRIC-OXIDE SYNTHASE ACTIVITY

Background: Bisacodyl and colchicine affect smooth-muscle contractilit y, intestinal water, and electrolyte transport. Nitric oxide (NO) stim ulates intestinal electrolyte secretion and has an important role as a mediator of intestinal motility. We therefore studied, in rats, the e ffects of these agents on nitric oxide synthase (NOS) activity and gas trointestinal transit. Methods: Rats were treated with bisacodyl (10 m g/kg intragastrically) or colchicine (5 mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg intragastrically). Rat s were killed after 1, 2, and 4 h. The intestine was isolated and rins ed, the mucosa scraped, and NOS activity determined. In all rats small -intestinal transit was measured 15 min after intragastric administrat ion of charcoal. Results: Bisacodyl (10 mg/kg) and colchicine (5 mg/kg ) induced a significant decrease in jejunal NOS activity. Pretreatment with the mast cell stabilizer ketotifen, which has been shown to atte nuate the increased permeability induced by NO inhibition, prevented t he decrease in colonic and jejunal NOS activity induced by bisacodyl a nd colchicine. Bisacodyl and colchicine significantly decreased intest inal transit time. Their effect on transit time was similar to that in duced by intravenous administration of N-G-nitro-L-arginine methyl eat er (10 mg/kg). Conclusions: It is suggested that the effect of bisacod yl and colchicine on intestinal transport is, at least partly, mediate d through NO inhibition.