TY - JOUR
T1 - Enhanced gastric ghrelin production and secretion in rats with gastric outlet obstruction
AU - Iwasaki, Eisuke
AU - Suzuki, Hidekazu
AU - Masaoka, Tatsuhiro
AU - Nishizawa, Toshihiro
AU - Hosoda, Hiroshi
AU - Kangawa, Kenji
AU - Hibi, Toshifumi
N1 - Funding Information:
Acknowledgments 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).
PY - 2012/4
Y1 - 2012/4
N2 - 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). Results 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. Conclusion GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.
AB - 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). Results 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. Conclusion GOO stimulates ghrelin dynamics and then enhances the mechanistic expression of gastric cellular communication network molecules between nerves and smooth muscle cells.
KW - Gastric emptying
KW - Gastric outlet obstruction
KW - Ghrelin
KW - Motility
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U2 - 10.1007/s10620-011-1953-y
DO - 10.1007/s10620-011-1953-y
M3 - Article
C2 - 22052447
AN - SCOPUS:84864055416
SN - 0163-2116
VL - 57
SP - 858
EP - 864
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
IS - 4
ER -
