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This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/G1052    most recent 00268.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Martinsen, T. C. Articles by Waldum, H. L. Search for Related Content PubMed PubMed Citation Articles by Martinsen, T. C. Articles by Waldum, H. L.

HORMONES AND SIGNALING

Ciprofibrate stimulates the gastrin-producing cell by acting luminally on antral PPAR-

¹Faculty of Medicine, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology and Department of ³Clinical Pharmacology and ²Medicine, St. Olav's Hospital HF, Trondheim University Hospital, Trondheim, Norway

Submitted 9 June 2005 ; accepted in final form 10 August 2005

The lipid-lowering drug ciprofibrate stimulates gastrin-producing cells in the rat stomach without lowering gastric acidity. Although suggested to be a luminal action on antral peroxisome proliferator-activated receptor- (PPAR-), the mechanism is still not fully elucidated. Gastric bypass was surgically prepared in male Sprague-Dawley rats. Gastric-bypassed and sham-operated rats were either given ciprofibrate (50 mg·kg^–1·day^–1 in methocel) or vehicle alone for 7 wk. PPAR- knockout (KO) and wild-type (WT) mice were either given ciprofibrate (500 mg·kg^–1·day^–1 in methocel) or vehicle alone for 2 wk. The concentration of gastrin in blood was analyzed. Antral G cell density and gastrin mRNA abundance were determined by using immunostaining and Northern blot analysis. Ciprofibrate did not raise plasma gastrin or G cell density in gastric-bypassed rats, although the gastrin mRNA level was slightly increased. In contrast, ciprofibrate induced hypergastrinemia, a 50% increase in G cell density, and a threefold increase in gastrin mRNA in sham-operated rats. In PPAR- KO mice, ciprofibrate did not raise G cell density or the gastrin mRNA level. The serum gastrin level was reduced by ciprofibrate. In WT mice, ciprofibrate induced hypergastrinemia, a doubling of G cell density, and a threefold increase in gastrin mRNA. Comparing animals dosed with vehicle only, PPAR- KO mice had higher serum gastrin concentration than WT mice. We conclude that the main effects of ciprofibrate on G cells are mediated from the antrum lumen, and the mechanism is dependent on PPAR-. The results indicate that PPAR- may have a role in the physiological regulation of gastrin release.

peroxisome proliferator-activated receptor-; hypergastrinemia; gastric bypass; peroxisome proliferator-activated receptor- knockout mice