Indomethacin accelerates clearance of labeled cells and increases DNA synthesis in gastrointestinal mucosa of the rat

Sprague-Dawley rats treated with placebo, parenteral indomethacin, or oral prostaglandin E₂ for six days were given an intraperitoneal injection of ³H]methyl-thymidine and killed at 45 min and 96 hr after labeling. Treatments were continued, until death. The dpm/DNA index was determined in mucosal scrapings of the stomach, duodenum, and jejunum and used to estimate DNA synthesis (45 min) and the clearance of labeled cells (96 hr). Indomethacin increased the DNA synthesis in both the duodenal and jejunal mucosa (P<0.05). In comparison to the controls, the clearance of labeled cells from the antral, duodenal, and jejunal mucosa was accelerated by indomethacin treatment, whereas the elimination of labeled cells from the antral and jejunal mucosa was slowed by PGE₂ treatment (P<0.05). DNA synthesis of the antral mucosa was significantly reduced by PGE₂ (P<0.05). The cyclooxygenase blocker did not affect the cell kinetic parameters of the oxyntic mucosa. The plasma levels of somatostatin were significantly higher both in PGE₂- and indomethacin-treated rats than in controls (P<0.05). It is concluded that indomethacin treatment increases the cell losses from the epithelial surface, which in turn trigger a compensatory trophic reaction. It is suggested that an important physiological action of endogenous prostaglandins is to regulate the outflow of cells from the superficial zones of the epithelium. Finally, this study disclosed the presence of hitherto unknown regulatory mechanism that promote cell proliferation in the gastrointestinal, mucosa despite inhibition of the synthesis of endogenous prostaglandins.