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Am J Physiol Gastrointest Liver Physiol (March 18, 2005). doi:10.1152/ajpgi.00298.2004
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Submitted on July 9, 2004
Accepted on March 8, 2005

Enhanced Ghrelin Secretion in Rats with Cysteamine-induced Duodenal Ulcers

Seiichiro Fukuhara1, Hidekazu Suzuki1*, Tatsuhiro Masaoka1, Mamoru Arakawa1, Hiroshi Hosoda2, Yuriko Minegishi3, Kenji Kangawa2, Hiromasa Ishii4, Masaki Kitajima5, and Toshifumi Hibi4

1 Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan; Center for Integrated Medical Research, Keio University School of Medicine, Tokyo, Japan
2 Department of Biochemistry, National Cardiovascular Center Research Institute, Osaka, Japan
3 Center for Integrated Medical Research, Keio University School of Medicine, Tokyo, Japan
4 Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
5 Department of Surgery, Keio University School of Medicine, Tokyo, Japan

* To whom correspondence should be addressed. E-mail: hsuzuki{at}sc.itc.keio.ac.jp.

Ghrelin, produced and secreted by the A-like cells of the stomach, stimulates growth hormone secretion, gastric motility, and food intake. Cysteamine inhibits the release of somatostatin and induces the formation of duodenal ulcers in rats. The present study was conducted to investigate the dynamics of ghrelin secretion in rats treated with cysteamine. Male Wistar rats (7-weeks-old) were administered three doses of cysteamine (400 mg/kg) orally; at fifty hours after the first dose, duodenal ulcers were induced, and the plasma level of somatostatin and gastric density of somatostatin-immunoreactive cells were significantly reduced. The plasma total and active ghrelin levels were significantly higher in the cysteamine-treated rats than in the control rats, while the gastric ghrelin levels, number of gastric ghrelin-immunoreactive cells, and preproghrelin mRNA expression levels were significantly lower. Even at the timepoints of 2 and 10 hours after the first dose of cysteamine, at which no significant ulcer formation or antral neutrophil accumulation was yet noted, a significant increase in the plasma ghrelin level and decrease in the gastric ghrelin level were observed. Furthermore, although lansoprazole treatment attenuated the duodenal ulceration induced by cysteamine, the increase in the plasma level of ghrelin could still be demonstrated. Since an inverse correlation was found between the plasma ghrelin and somatostatin levels, the inhibition of somatostatin secretion may be associated with the increased ghrelin secretion. In conclusion, an increase in the plasma ghrelin level precedes the formation of duodenal ulcers in rats treated with cysteamine.




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