S1663 Enhanced Ghrelin Production and Secretion and Reduced Expression of Ghrelin Receptor in Rat Stomach with Delayed Gastric Emptying

Abstract

Background. Ghrelin is a gastrointestinal peptide that stimulates growth hormone secretion, food intake, body weight gain and upper gastrointestinal motility. Ghrelin has distinct effects on gastrointestinal motility, which may be mediated through the growth hormone secretagogue receptor (GHS-R) on the vagus nerve and enteric nerve endings. We previously reported that plasma ghrelin levels were significantly higher in patients with dysmotilitylike functional dyspepsia (Aliment Pharmacol Ther. S4:104-110, 2006). Plasma ghrelin was also increased in obese patients after gastric banding operation (Obese Surg. 15, 1024-9, 2005). The aim of the present study was to investigate the influence of delayed gastric emptying caused by surgical manipulation on the dynamics of ghrelin and GHS expression in rats.Methods. 7-week-old male Sprague-Dawley rats with or without duodenal strictures were used as models of delayed gastric emptying. After 24 hours' fasting, the rats were divided into two groups, as follows; Control group (n=14; sham operation with abdominal incision alone), impaired gastric emptying group (n=14; proximal duodenal stricture with an 18 Fr.-Nelaton catheter) As weight loss is known to increase the circulating levels of ghrelin, a pair-feeding method was applied to equalize the body weight. Rats were sacrificed 2 weeks after the operation after the 24 hours' food deprivation. Gastric emptying rate was evaluated by the phenol red method. Plasma and gastric levels of ghrelin levels were measured by radioimmunoassay. Gastric expressions of preproghrelin mRNA and GHS-R mRNA were evaluated by quantitative RT-PCR, and immunohistochemistry was performed to determine gastric ghrelin localization. Results. No significant differences in the body weight were observed among two groups. The gastric emptying rate in groups with duodenal stricture was significantly lower compared with control group (9.8%, 61.0%, p<0.05). Rats with duodenal strictures showed significant increase in the preproghrelin mRNA expression (p<0.05) and density of ghrelin positive cells in the stomach (p<0.01), significant decrease of gastric total ghrelin levels (p<0.05), and increase of the plasma total ghrelin levels (p<0.01), while they showed a significant decrease in the levels of GHS-R mRNA expression (p<0.05). Conclusion. The present study has provided the first evidence that production and secretion of gastric ghrelin is enhanced in rats with delayed gastric emptying. It suggests that deregulation of gastric accommodation and emptying would induce the enhancement of ghrelin dynamics and the down-regulation of GHS-R.