Role of polyamines in intestinal adaptation in the rat

Abstract

The cellular mechanisms controlling adaptive intestinal mucosal hypo- and hyperplasia are poorly understood but changes in tissue polyamine levels and in the activity of the key enzymes controlling their synthesis (ornithine decarboxylase: ODC) and degradation (diamine oxidase: DAO) have been implicated. Therefore, in two models of adaptive mucosal hyperplasia (pancreatico-biliary diversion, PBD, achieved by surgically transposing the jejunum to lie between pylorus and ampulla of Vater, and 90% small bowel resection, SBR-both studied 8 weeks after surgery) and in one model of hypoplasia (8 days total parenteral nutrition) we measured indices of mucosal mass (wet weight, protein and DNA per 10-cm intestine), the growth-associated polyamines (putrescine, spermidine and spermine per 10-cm intestine and per mg DNA) and DAO activity in the duodenum, five 10-cm segments of jejunum, five 10-cm segments of ileum and in the colon, and compared the results with those found in transected or unoperated controls. The results for the indices of mucosal mass confirmed that TPN led to a modest degree of small bowel mucosal hypoplasia whilst PBD, and particularly 90% SBR, stimulated marked adaptive hyperplasia. There were corresponding changes in the amounts of putrescine and spermidine (but not of spermine)-not only when the results were expressed per unit length but also when calculated per mg mucosal DNA and in the ratio of spermidine:spermine. There was an increasing proximal-to-distal gradient in mucosal DAO per unit length intestine in all experimental groups but when the results were expressed per mg DNA, the ileal DAO levels were significantly reduced in the PBD and resection groups, when compared with the controls. These data support the hypothesis that polyamines play a major, and perhaps a controlling, role in regulating adaptive intestinal mucosal growth.