Effect of colchicine and bisacodyl on rat intestinal transit and nitric oxide synthase activity.
BACKGROUND
Bisacodyl and colchicine affect smooth-muscle contractility, intestinal water, and electrolyte transport. Nitric oxide (NO) stimulates intestinal electrolyte secretion and has an important role as a mediator of intestinal motility. We therefore studied, in rats, the effects of these agents on nitric oxide synthase (NOS) activity and gastrointestinal transit.


METHODS
Rats were treated with bisacodyl (10 mg/kg intragastrically) or colchicine (5 mg/kg intraperitoneally) with or without pretreatment with ketotifen (1 mg/kg intragastrically). Rats were killed after 1, 2, and 4 h. The intestine was isolated and rinsed, the mucosa scraped, and NOS activity determined. In all rats small-intestinal transit was measured 15 min after intragastric administration 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 attenuate the increased permeability induced by NO inhibition, prevented the decrease in colonic and jejunal NOS activity induced by bisacodyl and colchicine. Bisacodyl and colchicine significantly decreased intestinal transit time. Their effect on transit time was similar to that induced by intravenous administration of NG-nitro-L-arginine methyl ester (10 mg/kg).


CONCLUSIONS
It is suggested that the effect of bisacodyl and colchicine on intestinal transport is, at least partly, mediated through NO inhibition.
Karmeli
F
F
Dept. of Medicine, Hadassah University Hospital, Mount Scopus, Jerusalem, Israel.
Stalnikowicz
R
R
Rachmilewitz
D
D
D000818:Animals; D001726:Bisacodyl / Q000494:pharmacology*; D003078:Colchicine / Q000494:pharmacology*; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D005772:Gastrointestinal Transit / Q000187:drug effects* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000201:enzymology; D007665:Ketotifen / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
D005765:Gastrointestinal Agents; D001726:Bisacodyl; D019001:Nitric Oxide Synthase; D003078:Colchicine; D007665:Ketotifen