EFFECTS OF GASTROPROKINETIC AGENTS ON GASTROPARESIS IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

The influence of diabetic hyperglycemia on solid gastric emptying in r ats was examined. Diabetes was produced by streptozotocin (STZ, 40 mg/ kg i.v.), and diabetic hyperglycemia was observed from 1 day after the STZ injection. The gastric emptying of glass beads in the diabetic ra ts was significantly delayed compared with that in age-matched control rats at 1, 3 and 7 days after diabetes induction. A slight decrease i n gastric emptying was observed in the diabetic rats from 2 to 52 week s after the diabetes induction. We also investigated the influence of gastroprokinetic agents on STZ-induced diabetic gastroparesis and subd iaphragmatic vagotomy-induced gastroparesis in rats. The selective 5-H T3 receptor antagonists ramosetron (YM060), YM114 (KAE-393), granisetr on and ondansetron, and the substituted benzamides (5-HT4 receptor ago nist/5-HT3 receptor antagonists) cisapride mosapride and SC-53116 dose -dependently enhanced gastric emptying in normal rats. These compounds also reversed the impairment of diabetic gastroparesis rats at 7 days after the STZ injection, but higher doses were required. The solid ga stric emptying in subdiaphragmatic vagotomized rats was also delayed. Ramosetron and the substituted benzamides cisapride and zacopride part ially reversed the gastroparesis in the vagotomized rats. These result s suggest that acute hyperglycemia is important mechanism for the dela y of solid gastric emptying in diabetic rats. It is also suggested tha t selective 5-HT3 receptor antagonists and substituted benzamides enha nce gastric emptying not only in normal rats but also in diabetic and vagotomized rats.