The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and particularly the gastrin cell.
The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (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 rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell 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 mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.
Waldum
H L
HL
Department of Medicine, University Hospital of Trondheim, Norway.
Kvetnoi
I M
IM
Sylte
R
R
Schulze
B
B
Martinsen
T C
TC
Sandvik
A K
AK
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D058607:Fibric Acids; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005755:Gastrins / Q000097:blood / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006640:Histidine Decarboxylase / Q000235:genetics; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D019821:Simvastatin / Q000494:pharmacology; D013004:Somatostatin / Q000235:genetics; D013045:Species Specificity
D000924:Anticholesteremic Agents; D058607:Fibric Acids; D005755:Gastrins; D000960:Hypolipidemic Agents; D013004:Somatostatin; D002995:Clofibric Acid; D008148:Lovastatin; D019821:Simvastatin; D006640:Histidine Decarboxylase; C019304:ciprofibrate