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Oral administration of nonsteroidal antiinflammatory drugs induces gastroduodenal mucosal damage in experimental animals as well as in humans. The aim of the present study was to evaluate the effect of rectally administered nonsteroidal antiinflammatory drugs on gastric mucosal damage, as well as on mucosal prostaglandin E2 synthesis. Fasting male rats were treated intrarectally with 0.5 ml 1% NaHCO3 solution containing several concentrations of either indomethacin, aspirin, ibuprofen, diclofenac, ketoprofen, or sulindac and concomitantly received 1 ml of 150 mM HCL intragastrically. Control rats received intrarectally the vehicle only. After 4 h, lesions in the secretory part of the stomach were scored and mucosal prostaglandin E2 synthesis was determined by the ex vivo prostaglandin generation technique. Dose-dependent mucosal damage was observed in indomethacin- and diclofenac-treated rats. Ketoprofen damage did not show dose dependency. In sulindac- and aspirin-treated rats, as well as in controls, no damage was detected. All drugs induced a significant and comparable degree of inhibition of prostaglandin E2 synthesis. There was no correlation between the severity of the mucosal damage and the inhibition of prostaglandin E2 synthesis. The ulcerogenicity of rectally administered nonsteroidal antiinflammatory drugs is therefore not directly related to the degree of inhibition of prostaglandin E2 synthesis and is probably related to the specific chemical and pharmacokinetic properties of each individual drug.

The effect of misoprostol and cimetidine on gastric cell turnover was studied. Endoscopic biopsy specimens of fundic and antral mucosa were obtained from duodenal ulcer patients before and after 4 wk of therapy with cimetidine 1.2 g/day or misoprostol 800 micrograms/day. Biopsy specimens were incubated with [3H]thymidine. Glandular column length and number of labeled cells were determined after autoradiography. There was no significant difference in column length of antral or fundic glands before or after therapy with cimetidine and misoprostol. The number of antral and fundic labeled cells was significantly decreased after misoprostol treatment (3.6 +/- 0.3 and 4.6 +/- 0.4, mean +/- SE), as opposed to their respective number before therapy (6.9 +/- 0.5 and 8.3 +/- 0.8) (p less than 0.01). On the other hand, after treatment with cimetidine, the number of antral and fundic labeled cells was significantly higher (11.8 +/- 0.9 and 7.5 +/- 1.0, respectively) as compared with their number before therapy (5.7 +/- 0.5 and 5.6 +/- 0.6, respectively). The decreased gastric cell turnover induced by misoprostol indicates that the trophic effect of prostanoids on gastric mucosa is not due to an increase in cellular kinetics. The increased gastric cell turnover induced by cimetidine may contribute to its therapeutic effect in peptic ulcer disease.