Potentiating Hypergastrinemic Effect by the Peroxisome Proliferator Ciprofibrate and Omeprazole in the Rat

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Abstract
Profound inhibition of gastric acid secretion induces enterochromaffin-like (ECL) cell carcinoids due to hypergastrinemia. Peroxisome proliferators also lead to hypergastrinemia and ECL cell carcinoids but without reducing gastric acidity. Since the peroxisome proliferator ciprofibrate is still in use as lipid-reducing agent, and proton pump inhibitors are among the most commonly used drugs, we found it of 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. The drugs were given by gastric gavage once daily for 4 weeks to female rats. Blood was drawn by vein puncture before and at the end of the 4-week period for determination of gastrin by radioimmunoassay. At death the stomachs were removed, the antral mucosa homogenized, and the density of gastrin and somatostatin mRNA determined by Northern blot, using 32P-labelled probes. Omeprazole dosing increased serum gastrin 4-fold, ciprofibrate 5-fold, and the combination 24-fold. Serum gastrin during ciprofibrate dosing increased gradually, reaching significance after 14 days. Antral gastrin mRNA density increased similarly to the increase in serum gastrin, whereas antral somatostatin mRNA tended to be reduced in the omeprazole and increased in the ciprofibrate-dosed rats. A potentiating hypergastrinemic effect of the peroxisome proliferator ciprofibrate and the inhibitor of gastric acid secretion omeprazole is shown, indicating different mechanisms of action.