POTENTIATING HYPERGASTRINEMIC EFFECT BY THE PEROXISOME PROLIFERATOR CIPROFIBRATE AND OMEPRAZOLE IN THE RAT

Background: Profound inhibition of gastric acid secretion induces ente rochromaffin-like (ECL) cell carcinoids due to hypergastrinemia. Perox isome proliferators also lead to hypergastrinemia and ECL cell carcino ids but without reducing gastric acidity. Since the peroxisome prolife rator ciprofibrate is still in use as lipid-reducing agent, and proton pump inhibitors are among the most commonly used drugs, we found it o f interest to evaluate both the effect of a combination of these drugs on serum gastrin and the expression of gastrin and somatostatin mRNA in antral mucosa. Methods: The drugs were given by gastric gavage once daily for 4 weeks to female rats. Blood was drawn by vein puncture be fore and at the end of the 4-week period for determination of gastrin by radioimmunoassay. At death the stomachs were removed, the antral mu cosa homogenized, and the density of gastrin and somatostatin mRNA det ermined by Northern blot, using P-32-labelled probes. Results: Omepraz ole dosing increased serum gastrin 4-fold, ciprofibrate 5-fold, and th e combination 24-fold. Serum gastrin during ciprofibrate dosing increa sed gradually, reaching significance after 14 days. Antral gastrin mRN A density increased similarly to the increase in serum gastrin, wherea s antral somatostatin mRNA tended to be reduced in the omeprazole and increased in the ciprofibrate-dosed rats. Conclusion: A potentiating h ypergastrinemic effect of the peroxisome proliferator ciprofibrate and the inhibitor of gastric acid secretion omeprazole is shown, indicati ng different mechanisms of action.