Cimetidine and prostaglandin: evidence for different modes of action on the rat gastric mucosa.

We have previously shown that the prostaglandin analogue 15(R)15 methyl-prostaglandin E2 methyl ester (Me-PGE2) when administered at a dose of 50 microgram per kg significantly inhibits aspirin-induced gastric mucosal erosions in the rat. In this study we have investigated the effect of cimetidine under similar circumstances. Cimetidine in a dose of 50 mg per kg significantly inhibited gastric mucosal erosions induced by aspirin (192 mg per kg) in the rat, reducing the incidence from 70% of 20 rats to 9.5% of 21 rats, the mean lesion score was reduced from 9.3 +/- 2.1 (mean +/- SEM) to 0.4 +/- 0.3. We then compared the effect of the above doses of Me-PGE2 and cimetidine on gastric erosions induced by aspirin (192 mg per kg) with the hourly addition of 160 mM HCl. The incidence of erosions in the aspirin + HCl group was 100% of 20 rats (mean lesion score 27.4 +/- 2.4). This was not significantly reduced by cimetidine, the incidence being 90% of 20 rats (mean lesion score 19.7 +/- 3.4). The incidence of erosions in the presence of Me-PGE2 was significantly less than that in both the other groups, 13% of 23 rats, (mean lesion score 3.1 +/- 0.8) P less than 0.01 in both instances. These results suggest that, whereas cimetidine protects the gastric mucosa through acid inhibition, Me-PGE2 appears to have a protective effect independent of acid inhibition.