PPAR alpha stimulates the rat gastrin-producing cell.
The peroxisome proliferator (PP) ciprofibrate stimulates gastrin-producing cells (G-cells) in the rat stomach by an unknown mechanism, inducing hypergastrinemia and secondary enterochromaffin-like (ECL) cell hyperplasia. Ciprofibrate is a specific ligand for the nuclear peroxisome proliferator-activated receptor alpha (PPAR alpha). To see whether the effects of ciprofibrate could be imitated, rats were given another PPAR alpha ligand WY-14643 or the PPAR gamma ligand troglitazone by gastric intubations daily for 28 and 56 days. Troglitazone failed to raise gastrin levels. WY-14643 increased gastrin mRNA abundance, G-cell density and induced hypergastrinemia, but to a lesser extent than ciprofibrate. ECL cell parameters increased in proportion with the relative hypergastrinemia. Ciprofibrate and WY-14643 altered the levels of acyl CoA-oxidase mRNA and PPAR alpha mRNA in antrum, but had no effect in corpus. The PPAR alpha receptor was found in at least some G-cells by immunostaining. This study supports the hypothesis that PPAR alpha specific ligands could stimulate the G-cells by acting locally from the stomach lumen through antral PPAR alpha.
D000818:Animals; D002839:Chromans / Q000008:administration & dosage / Q000494:pharmacology; D002995:Clofibric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D058607:Fibric Acids; D005753:Gastric Mucosa / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000096:biosynthesis / Q000097:blood* / Q000187:drug effects; D008024:Ligands; D010295:Parietal Cells, Gastric; D020025:Peroxisome Proliferators / Q000008:administration & dosage / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000502:physiology*; D000077288:Troglitazone
D002839:Chromans; D058607:Fibric Acids; D005755:Gastrins; D008024:Ligands; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D002995:Clofibric Acid; C006253:pirinixic acid; C019304:ciprofibrate; D000077288:Troglitazone