Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis.

Abstract

Refeeding fasted rats induces a dramatic trophic response in gastrointestinal mucosa and is associated with elevations in both the rate of DNA synthesis and ornithine decarboxylase (ODC) activity. The signal for these increases is unknown. Amiloride prevents cell alkalinization by blocking Na+-H+ exchange at apical epithelial cell membranes. In study 1, rats were fasted 48 h, treated with amiloride (0.5 to 500 mg/kg), and refed for 4 h. Refeeding increased ODC activities in the jejunal mucosa (X8) and liver (X19) but not in the oxyntic gland mucosa. In the jejunum, but not the liver, the activation of ODC was completely abolished by 100 mg/kg amiloride. In study 2, the rate of DNA synthesis was determined by measuring the rate of [3H]thymidine incorporation 16 h after refeeding. Refeeding resulted in significantly increased rates of DNA synthesis (dpm.microgram DNA-1.30 min-1) over fasted levels, and amiloride at 100 mg/kg significantly reduced the elevations in the jejunum and liver. In conclusion, amiloride inhibits the postprandial increases in jejunal ODC activity and DNA synthesis in the jejunum and liver. The results indicate that 1) the Na+-H+ antiport is essential to the increased ODC activity in the jejunum and the stimulation of DNA synthesis in the jejunum and liver after a meal and 2) increases in DNA synthesis and their suppression by amiloride are not necessarily linked to ODC activity.