neuropeptide-y and Gastroesophageal-Reflux

Gastroesophageal reflux disease (GERD) is often associated with decreased upper gastrointestinal motility, and ghrelin is an appetite-stimulating hormone known to increase gastrointestinal motility. We investigated whether ghrelin signaling is impaired in rats with GERD and studied its involvement in upper gastrointestinal motility. GERD was induced surgically in Wistar rats. Rats were injected intravenously with ghrelin (3 nmol/rat), after which gastric emptying, food intake, gastroduodenal motility, and growth hormone (GH) release were investigated. Furthermore, plasma ghrelin levels and the expression of ghrelin-related genes in the stomach and hypothalamus were examined. In addition, we administered ghrelin to GERD rats treated with rikkunshito, a Kampo medicine, and examined its effects on gastroduodenal motility. GERD rats showed a considerable decrease in gastric emptying, food intake, and antral motility. Ghrelin administration significantly increased gastric emptying, food intake, and antral and duodenal motility in sham-operated rats, but not in GERD rats. The effect of ghrelin on GH release was also attenuated in GERD rats, which had significantly increased plasma ghrelin levels and expression of orexigenic neuropeptide Y/agouti-related peptide mRNA in the hypothalamus. The number of ghrelin-positive cells in the gastric body decreased in GERD rats, but the expression of gastric preproghrelin and GH secretagogue receptor mRNA was not affected. However, when ghrelin was exogenously administered to GERD rats treated with rikkunshito, a significant increase in antral motility was observed. These results suggest that gastrointestinal dysmotility is associated with impaired ghrelin signaling in GERD rats and that rikkunshito restores gastrointestinal motility by improving the ghrelin response.

Topics: Agouti-Related Protein; Animals; Drugs, Chinese Herbal; Duodenum; Eating; Gastric Emptying; Gastroesophageal Reflux; Gastrointestinal Motility; Ghrelin; Growth Hormone; Immunohistochemistry; Male; Neuropeptide Y; Plant Extracts; Polymerase Chain Reaction; Rats; Rats, Wistar; RNA; Signal Transduction; Stomach

The distribution of nerve fibers and cell bodies reactive for the peptides enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide were studied in biopsies of external muscle taken from the gastric body and antrum of 17 patients undergoing surgery for gastroesophageal reflux, and in regions of healthy stomach resected as part of gastric cancer operations. The results were correlated with preoperative measurements of liquid and solid emptying from the stomach in the patients with gastro-esophageal reflux. In three cases, no delay was detected in either liquid or solid emptying, and the distribution of peptide immunoreactive fibers in the external muscle was similar to that of healthy muscle. In 14 cases, the emptying of either liquids or solids or both was delayed, and in eight of these clearcut changes in the distribution of peptide-immunoreactive fibers occurred. In six cases, the number of enkephalin-immunoreactive fibers was fewer than normal in the biopsy from the gastric body (in one of these samples the number of substance P-immunoreactive fibers was also reduced). In another cae, the number of substance P-immunoreactive fibers in the antrum was reduced, and in another the number of vasoactive intestinal peptide and neuropeptide Y-immunoreactive fibers in the antral biopsy was reduced. It is concluded that in patients with gastroesophageal reflux who have delayed gastric emptying, a proportion demonstrate abnormalities of the peptide-immunoreactive fibers that innervate the gastric external muscle.

Topics: Enkephalins; Esophagus; Female; Fluorescent Antibody Technique; Gastric Emptying; Gastroesophageal Reflux; Humans; Male; Middle Aged; Nerve Fibers; Neuropeptide Y; Peristalsis; Stomach; Substance P; Vasoactive Intestinal Peptide

The occurrence and distribution of neuropeptide Y (NPY) was studied in smooth-muscle specimens from the human lower esophageal sphincter region by immunocytochemistry and immunochemistry. Normal individuals and patients suffering from achalasia or hiatus hernia with severe gastroesophageal reflux were examined. NPY fibers were found within and around smooth-muscle bundles of the longitudinal and the circular muscle layers and within the myenteric ganglia. Smooth-muscle specimens from patients with hiatus hernia and gastroesophageal reflux displayed numerous NPY fibers and an increased content of NPY. Specimens from patients with achalasia contained only few NPY fibers and had a decreased content of NPY as compared to specimens from control patients. Conceivably, NPY may play a role in the regulation of the lower esophageal sphincter.

Topics: Adolescent; Adult; Aged; Esophageal Achalasia; Esophageal Diseases; Esophageal Neoplasms; Esophagogastric Junction; Gastroesophageal Reflux; Hernia, Hiatal; Histocytochemistry; Humans; Middle Aged; Neuropeptide Y; Radioimmunoassay