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Prostaglandins have cytoprotective effects on gastric mucosa via the influence of various mechanisms. The purpose of this study is to examine the effects of prostaglandins on maturation-dependent spontaneous apoptosis in gastric mucosal cells in vitro, which mimics the apoptosis of gastric mucosal cells related with a rapid cell turnover rate in vivo. Both prostaglandin E1 and E2 inhibited spontaneous apoptosis in a dose-dependent manner and increased the viability of gastric mucosal cells in culture. A number of antiulcer drugs presently in clinical use were shown to increase the concentrations of prostaglandins in cells. All of the drugs tested clearly inhibited the spontaneous apoptosis in a dose-dependent manner. Based on these results, we propose that the cytoprotective effects of prostaglandins on gastric mucosa in vivo can be partially explained by an increase in the number of gastric mucosal cells present as a result of the inhibition of maturation-dependent spontaneous apoptosis.
KEY WORDS: spontaneous apoptosis; gastric mucosal cells; anti-ulcer drugs; prostaglandins.
Prostaglandins (PGs), one of the major groups of chemical mediators in the mammalian body, are involved in numerous physiological reactions, such as inflammation and cellular differentiation (1). PGs, especially PGE1 and PGE2, also have cytoprotective effects on gastric mucosa as a consequence of various physiological mechanisms that include increased epithelial mucus secretion (2) and amelioration of mucosal blood flow (3). Cyclooxygenase, the first enzyme in the pathway of PG synthesis from arachidonic acid, exists in both constitutive (cyclooxygenase-1) and inducible (cyclooxygenase-2) isoforms (4). While PGs produced by cyclooxygenase-2 (cox-2) seem to be involved in inflammation and cellular differentiation, PGs produced by cyclooxygenase-1 (cox-1) may be involved in cytoprotective effects on gastric mucosa (5).
Gastric mucosal cells (gastric pit cells) have a rapid rate of turnover in vivo. This short turnover cycle is the result of rapid proliferation of progenitor cells at the isthmus, cell maturation that occurs during the upward migration of cells, and rapid cell death at the gastric surface (6). In the normal mammalian stomach, there is a balance between the proliferation of progenitor cells and the death of mature cells at the gastric surface. Alterations in this balance due to various pathological conditions in gastric mucosa have been reported (7, 8). For example, changes in the balance between the proliferation and...