Effect of dietary polyamines and alpha-difluoromethylornithine on regulation of intestinal Na+/H+ exchanger

Polyamines are compounds required for initiation of rapid cellular growth and differentiation in many cell types. Ornithine decarboxylase is the rate limiting enzyme in polyamine synthesis. Fasting and refeeding regulates the activity of ornithine decarboxylase and polyamine content in the intestinal tract. We tested the hypothesis that polyamines regulate cell growth via the Na+/H+ exchanger which is believed to be intimately involved in cell growth. Ileal Na+/H+ activity was therefore examined in control, fasted, refed fasted, and in rats given the specific inhibitor of ornithine decarboxylase alpha-difluoromethylornithine. A well-validated ileal brush border membrane vesicles for the study of Na+/H+ exchange activity was utilized. Fasting markedly decreased while refeeding stimulated Na+/H+ exchange activity at all times studied (P less than 0.05-0.001). Maximal uptake of Na+ at 5 min was 3.12 +/- 0.05, 2.5 +/- 0.05 and 2.22 +/- 0.05 nmol/mg protein in refed, control and fasted rats respectively. Kinetics of amiloride sensitive Na+/H+ exchanger showed a Vmax of 17.1 +/- 3.5, 8.0 +/- 0.64 and 4.7 +/- 1.1 nmol/mg protein per 5 s in refed fasted, control and fasted rats respectively Km values were not significantly different between the groups studied. 2% alpha-difluoromethylornithine given in the drinking water abolished the stimulation in Na+/H+ exchange activity in refed fasted rats. These results suggest a close relationship between polyamines and Na+/H+ activity in the intestinal mucosa of rats.