Polyamines in the response to intestinal obstruction.

The gastrointestinal mucosa immediately proximal to an intestinal obstruction becomes hyperplastic. Since mucosa that is distal to an obstruction atrophies, it appears that the adaptational response to obstruction is regulated by local factors. The hypothesis tested in these studies is that increased polyamine metabolism in the gut proximal to an obstruction is a required local event in the hyperplastic process. Ligation of either rat ileum or colon resulted within 66 h in a doubling of total RNA, DNA, and protein content in the 2 cm of mucosa immediately proximal to the tie. The trophic response was accompanied by an increase in primary amine content of the intestinal chyme in the segment of gut under investigation. These amines were not removed from intestinal chyme by 24 h of lyophilization, suggesting that the more volatile short-carbon-chain aliphatic amines were of limited importance. Subsequent studies focused on polyamine metabolism. Ornithine decarboxylase (ODC) activity was increased in the mucosa proximal to obstruction. In the ileum, ODC activity was increased 10-fold over control values and in the colon about 2-fold. Increased ODC activity was accompanied by corresponding increases in mucosal polyamine content. Finally, treatment of rats with difluoromethylornithine, a selective, irreversible inhibitor of ODC, partially prevented the trophic response to intestinal obstruction.