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. 1990 Nov;116(6):629–632. doi: 10.1007/BF01637085

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

H Weiler 1,✉, U Moser 1, W Gerok 1
PMCID: PMC12201082  PMID: 2254381

Abstract

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-PGF1α generation and the amounts of these prostaglandins in the intestinal contents were significantly lowered. However, PGD2 and 6-keto-PGFα jejunal release, and the amounts of these prostaglandins found in the intestinal contents, were already low after a subletal 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 siginificantly inhibited by indomethacin. The increased jejunal synthesis of PGE2, with its enteropooling effect, may play a significant role in methotrexate-induced diarrhea in rats.

Key words: Methotrexate, diarrhea, Small intestine, Prostaglandin, rat

Abbreviation

PGE2, PGD2, PGI2

prostaglandins E2, D2, I2

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