Teruyuki Tanaka

Histamine Mediates the Stimulatory Action of Ghrelin on Acid Secretion in Rat Stomach

Ghrelin, a novel growth hormone-releasing peptide, is present in the rat and human stomach and is known to stimulate acid secretion and stomach motility. However, the mechanism of action of ghrelin is not fully understood. In the present study, we attempted to elucidate the role of histamine in ghrelin-induced acid secretion in rat stomach. Intravenous administration of ghrelin at 0.8 to 20 μg/kg dose dependently increased gastric acid secretion, as measured by the gastric lumen perfusion method. The maximum response was almost equal to that of gastrin (20 μg/kg). These actions were abolished by bilateral subdiaphragmatic vagotomy. Famotidine (0.33 mg/kg) also completely inhibited the effects of ghrelin. Furthermore, ghrelin increased histidine decarboxylase (HDC) messenger RNA (mRNA) levels, as measured by real-time reverse transcription-polymerase chain reaction using LightCycler. The action of ghrelin on HDC mRNA was abolished by vagotomy. Ghrelin did not affect histamine release from isolated vascularly perfused rat stomach. Taken together, these results suggest that ghrelin stimulates gastric acid secretion via a mechanism involving activation of vagal efferent nerve and histamine release from gastric enterochromaffin-like cells.

Expression of c-Fos protein in the brain after intravenous injection of ghrelin in rats

In this study, we surveyed central neurons that might be activated after peripheral administration of a gut-brain peptide ghrelin, by examining neurons expressing c-Fos protein. First, we examined the relationship between the dose of ghrelin and the amount of gastric acid secreted. Ghrelin induced a significant increase in the amount of gastric acid secretion in a dose-dependent manner. Secondly, we examined central neurons that expressed c-Fos protein after intravenous injection of ghrelin. We found that intravenously injected ghrelin induced the neural expression of c-Fos protein in several nuclei and circumventricular organs in the brain. These results suggest that ghrelin released into the circulation may stimulate central neurons that have some role in the control mechanism for gastric acid secretion.

Effect of interleukin-8 on histamine release from totally isolated vascularly perfused rat stomach

BackgroundRecent studies have demonstrated relationships between cytokines and gastric acid secretion. The present study was performed in rats to elucidate the effects of interleukin-8 (IL-8) on gastric acid secretion through an increase in histamine release from the stomach.MethodsThe experiments were performed in gastric lumen-perfused rats for the study of acid secretion and in totally isolated vascularly perfused rat stomach preparations for the study of histamine release. The histamine in the effluent was determined by radioimmunoassay.ResultsIL-8 (500 ng) significantly enhanced gastrin-stimulated acid secretion. IL-8, at a concentration of 500 ng/20 ml per 10 min, did not alter basal histamine release, but at 100 ng/20 ml and 500 ng/20 ml it dose-dependently increased gastrin-stimulated histamine release.ConclusionsIL-8 enhances gastrin-stimulated acid secretion and histamine release from the rat stomach, which may explain the enhancing effect of IL-8 on gastric acid secretion.