Enhanced Gastric Ghrelin Production and Secretion in Rats with Gastric Outlet Obstruction
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Background and Aim
Ghrelin has distinct effects on gastrointestinal motility through the vagus nerve and gastric excitatory neural plexus. The objectives of this study were to investigate the dynamics of ghrelin and expression of neuromuscular markers in a newly established surgically manipulated rat model of gastric outlet obstruction (GOO), akin to the pyloric stricture associated with duodenal ulcer, advanced gastric cancer, and other conditions, in the clinical setting.
Material and Methods
The rats were divided into two groups, a control group (sham operation) and the GOO group (proximal duodenal stricture). The animals were sacrificed 2 weeks after the operation. Plasma and gastric ghrelin were measured by radioimmunoassay. mRNA expression in the stomach of neural choline acetyltransferase (ChAT), c-kit, and membrane-bound stem cell factor (SCF) were analyzed by quantitative RT-PCR. In addition, gastric mRNA expression of the aforementioned were also evaluated 60 min after intraperitoneal administration of a synthetic GHS-R1a antagonist ([d-Lys3] GHRP-6 6.0 mg/kg).
Mechanical GOO induced increases of fasting plasma ghrelin levels and hyperplasia of the gastric muscle layers, with enhanced expression of the gastric neuromuscular markers. Administration of [d-Lys3] GHRP-6 normalized the enhanced expression of c-kit and SCF.
GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.
KeywordsGhrelin Gastric emptying Motility Gastric outlet obstruction
This work was supported in part by a Grant-in-Aid for Young Scientists (B) from the Japan Society for the Promotion of Science (no. 18790471 to EI), a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (no. 22300169, to HS), a Health and Labour Sciences Research Grant for Research on Health Technology Assessment (Clinical Research Promotion no. 47 to HS), a grant from the JSPS Bilateral Joint Projects with Belgium (11035231-000061), a grant from the Smoking Research Foundation (to HS), the Keio Gijuku Academic Development Fund (to HS), and a Nateglinide Memorial Toyoshima Research and Education Fund (to HS).
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