Antral G cells in rats during dosing with a PPAR alpha agonist: a morphometric and immunocytochemical study.
Gastrin-producing G cells constitute one of the major populations of neuroendocrine cells in the antral mucosa of the stomach. The peroxisome proliferator-activated receptor (PPAR) alpha-agonist ciprofibrate is used as a lipid-lowering drug. Recently, ciprofibrate has been shown to induce hypergastrinemia in rats without reducing gastric acidity, which indicates a direct stimulatory effect on the G cell. Gastrin probably plays an important role in gastric tumorgenesis, and long-term dosing with ciprofibrate results in enterochromaffin-like (ECL) cell carcinoids in the oxyntic mucosa of rats. In this study, we aimed to examine changes of neuroendocrine granules in G cells following ciprofibrate dosing and relate them to changes induced by the proton pump inhibitor pantoprazole. Furthermore, we wanted to study peroxisomes in G cells. Rats received ciprofibrate 80 mg/kg/day or pantoprazole 200 mg/kg/day in 4 weeks. Antral mucosal specimens were processed for conventional staining procedures and immunocytochemistry for both the light and electron micro-scope. Specimens were immunolabeled for gastrin and peroxisome-specific proteins. Electron micrographs were analyzed planimetrically. This study shows that hypergastrinemia induced by ciprofibrate is accompanied by a decrease in granule number per cell and a relative increase in electron-dense granules. These changes were quite similar to those induced by pantoprazole, indicating signs of G-cell activation in general. However, distinctions concerning granule size and composition and both hypertrophy and hyperplasia of G cells are presented. Finally, demonstration of peroxisomes in G cells was only achieved by using the highly sensitive tyramide signal amplification technique in immunostaining for the peroxisome-specific protein PMP-70. Therefore, neither morphological nor quantitative changes of peroxisomes in G cells were detected.
Martinsen
Tom C
TC
Institute of Intra-abdominal Diseases, Faculty of Medicine, Norwegian University of Science and Technology, MTFS, 7489 Trondheim, Norway. tom.chr.martinsen@medisin.ntnu.no
Skogaker
Nan E T
NE
Bendheim
Marianne Ø
MØ
Waldum
Helge L
HL
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002995:Clofibric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D058607:Fibric Acids; D019863:Gastrin-Secreting Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D005755:Gastrins / Q000096:biosynthesis / Q000097:blood; D007150:Immunohistochemistry; D008297:Male; D016253:Microscopy, Immunoelectron; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D020025:Peroxisome Proliferators / Q000494:pharmacology; D020675:Peroxisomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D054328:Proton Pump Inhibitors; D011706:Pyloric Antrum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D013454:Sulfoxides / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D058607:Fibric Acids; D005755:Gastrins; D020025:Peroxisome Proliferators; D054328:Proton Pump Inhibitors; D018160:Receptors, Cytoplasmic and Nuclear; D013454:Sulfoxides; D014157:Transcription Factors; D002995:Clofibric Acid; D000077402:Pantoprazole; C019304:ciprofibrate; D009853:Omeprazole