Effect of methotrexate on the release of prostaglandins E2, D2, and I2 from small intestine in the rat in vivo.

Intraperitoneal administration of methotrexate in a single dose of 40 mg/kg induces fluid accumulation in the small intestine of rats, significantly increasing jejunal PGE2 formation and simultaneously the amounts of PGE2 in the intestinal contents in vivo. Concomitantly, jejunal PGD2 and 6-keto-PGF1 alpha generation and the amounts of these prostaglandins in the intestinal contents were significantly lowered. However, PGD2 and 6-keto-PGF1 alpha jejunal release, and the amounts of these prostaglandins found in the intestinal contents, were already low after a sublethal dose (4 mg/kg) of methotrexate, whereas the jejunal release as well as the amounts in the intestinal contents of PGE2 were not altered. Fluid accumulation, the amounts of prostaglandins in the intestinal contents and jejunal release of prostaglandins are significantly inhibited by indomethacin. The increased jejunal synthesis of PGE2, with its enteropooling effect, may play a significant role in methotrexate-induced diarrhea in rats.