EFFECTS OF LONG-TERM TREATMENT WITH ANTHRANOIDS AND SODIUM PICOSULPHATE ON THE CONTENTS OF VASOACTIVE INTESTINAL POLYPEPTIDE, SOMATOSTATIN AND SUBSTANCE-P IN THE RAT COLON

Objective: To examine the effects of chronic treatment and a single hi gh-dose application of anthranoids and sodium picosulphate on the neur opeptide content of the rat colon. Design and Methods: Over a 6-month period, eight groups of rats were each given one of the following: sen nosides or sodium picosulphate in low daily doses (10 and 2.5 mg/kg/da y, respectively), in high daily doses (40 and 10 mg/kg/day, respective ly), and in high twice-weekly doses (30 and 7.5 mg/kg/day, respectivel y); high daily doses of danthron (500 mg/kg/day); and vehicle (tragaca nth 0.5%) only. Four further groups of rats each received a single dos e of vehicle or a high dose of one of the three laxatives. All rats we re killed 48 h after the last dose. The ascending and descending colon were removed and separated into mucosa, submucosa, and muscularis ext erna. Vasoactive intestinal polypeptide (VIP), somatostatin, and subst ance P were extracted by boiling and homogenizing the tissue in acetic acid, and their levels were determined using validated radioimmunoass ays. Results: After long-term treatment with high doses of sennosides and danthron, but not after a single high-dose administration, there w as a significant reduction in mucosal levels of VIP and somatostatin a nd in submucosal levels of somatostatin of both colonic segments, as w ell as in the level of VIP in the muscularis externa of the descending colon. Substance P levels remained unaffected. Sodium picosulphate ha d no effect. Conclusions: Chronic treatment with anthranoids in high d oses, but not with sodium picosulphate, reduces VIP and somatostatin l evels in the rat colon. This may represent damage to the enteric nervo us tissue or a pharmacological effect of the anthranoids, causing decr eased synthesis or increased breakdown of these peptides.