AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 3 408-G415, Copyright © 1988 by American Physiological Society
Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis
M. G. Ulrich-Baker, P. Wang, L. Fitzpatrick and L. R. Johnson
Department of Physiology and Cell Biology, University of Texas Health Science Center, Houston 77225.
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.
