THE EFFECT OF THE PEROXISOME PROLIFERATOR CIPROFIBRATE ON THE GASTRIC-MUCOSA AND PARTICULARLY THE GASTRIN CELL

The peroxisome proliferator ciprofibrate induces hypergastrinemia with out inhibiting acid secretion. The present study was carried out to as sess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrat e with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radio-immunoassay method, G cell density by histomorphometry after i mmunostaining for G cells, and gastrin, somatostatin and histidine dec arboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrat e (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P <0.01) in male and female Fischer rats as well as in female Wistar rat s. Simvastatin and lovastatin did not affect serum gastrin. Antral G c ell density increased significantly in female Wistar rats (P<0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucose increased markedly an d significantly (P<0.01) after ciprofibrate treatment. The present stu dy shows that the peroxisome proliferator ciprofibrate induces hyperga strinemia secondary to an increased storage and synthesis of antral ga strin. Since somatostatin mRNA abundance also increased, the present s tudy suggests that ciprofibrate and possibly other peroxisome prolifer ators in sufficient concentrations have a stimulatory effect on endocr ine cells.