Prostaglandin-mediated trophic effects on the rat duodenum: the role of polyamines

Ornithine decarboxylase (ODC) is the initial rate-limiting enzyme in polyamine biosynthesis. The relationship between ODC and polyamines and the trophic effect of prostaglandin in the rat gastrointestinal tract are unknown. In these studies we determined whether inhibition of ODC activity and subsequent polyamine biosynthesis with the specific enzyme inhibitor difluoromethyornithine (DFMO) would attenuate prostaglandin-mediated trophic effects in the rat duodenum. Significant increases in duodenal mucosal wet weight, RNA, DNA, and protein were found following treatment with 16,16-dimethyl-PGE2 (1 mg/kg) for 1 week. This trophic response was significantly reduced (P less than 0.01) in the duodenum of rats treated concomitantly with DFMO. In addition, this prostenoid significantly increased (4X) duodenal ODC levels, 2 hr following acute administration. These results suggest that polyamines are required for the prostaglandin-stimulated growth of the rat duodenal mucosa.