Inhibition of acid secretion and gastric lesions in rats by the prostanoid Ro 22-6923

Abstract

The synthetic prostanoid Ro 22-6923 was studied for its ability to inhibit gastric secretion and to protect the gastric mucosa against the injurious effects of stress, indomethacin and ethanol. Ro 22-6923 inhibited basal acid secretion when administered intragastrically or intraduodenally to animals with a gastric fistula. The pH of the gastric juice promptly increased and remained above 5 for 3 h after an intragastric dose of 10 micrograms/kg and the pH remained above 4 for more than 3 h after this dose given intraduodenally. The increase in pH was associated with reduction of acid concentration and H+ output. Ro 22-6923 inhibited histamine-stimulated gastric secretion in a perfused stomach preparation with an ED50 of 15 micrograms/kg compared to values of 43, 126 and 289 micrograms/kg for prostaglandin (PG)E2, ranitidine and cimetidine, respectively. The synthetic prostanoid protected the gastric mucosa from the injurious effects of stress (oral ED50 values of 0.2 and greater than 1.0 mg/kg for Ro 22-6923 and PGE2, respectively) and indomethacin (oral ED50 0.07 and 0.06 mg/kg for Ro 22-6923 and PGE2, respectively). Cimetidine and ranitidine, at high doses, were effective against the mucosal damage produced by stress (ED50 values greater than 100 mg/kg) and indomethacin (ED50 values greater than 10 mg/kg). Ro 22-6923, but not PGE2 or 16, 16-dimethyl PGE2, inhibited dibutyryl cyclic AMP-induced [14C]aminopyrine accumulation by isolated parietal cells, indicating that the prostanoid has a direct inhibitory effect on H+ secretion. The results on the antisecretory and cytoprotective properties of Ro 22-6923 suggest this drug could be potentially useful in the pharmacotherapy of peptic ulcer disease.