REGULATION OF TRANSGLUTAMINASE ACTIVITY BY POLYAMINES IN THE GASTROINTESTINAL MUCOSA OF RATS

Transglutaminases catalyze the covalent cross-linking of protein and a re involved in the mechanism of polyamine-dependent mucosal healing. T he current study examined the effect of polyamines on transglutaminase activity in gastrointestinal mucosa. Rats were fasted 22 hr before ex periments and enzyme activity was measured as the Ca++-dependent coval ent incorporation of [H-3]-putrescine into acid-precipitable protein. In some of the experiments, mucosal ornithine decarboxylase (ODC) acti vity and polyamine levels were also examined. Transglutaminase activit y in both gastric and duodenal mucosa increased significantly after po lyamine administration. Treatment with alpha-difluoromethylornithine ( DFMO) decreased both basal ODC activity and putrescine levels in the d uodenal mucosa. DFMO also significantly decreased mucosal transglutami nase activity. In stress or hypertonic NaCl-induced gastric mucosal in jury models, increased polyamine biosynthesis was associated with incr eased transglutaminase activity, which was completely prevented by DFM O. Exogenous polyamines returned transglutaminase activity toward cont rol levels in the presence of DFMO. In conclusion, these results indic ate that: (i) luminal polyamines increase transglutaminase activity in gastric and duodenal mucosa; (ii) polyamine depletion caused by the i nhibition of ODC is accompanied by a significant decrease in transglut aminase activity; and (iii) exogenous polyamines significantly reverse the decrease in transglutaminase activity caused by polyamine depleti on.