Effect of combined treatment with S-0509 (a selective CCK-B/gastrin receptor antagonist) and omeprazole on acetic acid-induced gastric ulcers in rats

• Published in: Japanese Journal of Pharmacology 2000, Vol.82 (suppl.1), p.67-67
• Main Authors: Kikuko Amagase, Mika Yokota, Hiromi Nakai, Kyoko Ikeda, Susumu Okabe
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Omeprazole significantly enhance the spontaneous healing of gastric ulcers and cause hypergastrinemia as the result of sustained acid inhibition. We examined whether or not such hypergastrinemia plays an important role in the mechanism underlying the enhanced ulcer healing by omeprazole. Acetic acid ulcers were induced in rats. IM (2 mg/kg × 1/day) was administered s.c. for 2 wks after ulceration. Omeprazole, with or without S-0509 (a selective gastrin receptor antagonist), was administered orally once a day for 2 wks after ulceration. The ulcer area, gastric secretory activity and serum gastrin level were determined thereafter. The antisecretory effects of these drugs were studied using a pylorus ligation preparation. The spontaneous healing of gastric ulcers was significantly enhanced by repeated treatment with S-0509, although the effect was not dose-related. The rate of healing was 65.2%, 36.0 %, and 66.7 % at 10, 30 and 60 mg/kg, respectively. Omeprazole also significantly enhanced ulcer healing, resulting in a rate of healing of 77.7% at 60 mg/kg. Gastric acid secretion in the animals was markedly inhibited by both S-0509 and omeprazole. The plasma gastrin level was significantly increased after treatment with S-0509 and omeprazole. The delayed ulcer healing induced by indomethacin was not affected by repeated treatment with S-0509. Nonetheless, the gastric acid secretion in the animals was inhibited. Combined treatment with omeprazole and S-0509 also significantly enhanced the ulcer healing and markedly inhibited the gastric acid secretion and increased the plasma gastrin level. It was suggested that the mechanism underlying the ulcer healing effect of omeprazole is unrelated to hypergastrinemia.