Central administration of ghrelin stimulates pancreatic exocrine secretion via the vagus in conscious rats.

Abstract

Ghrelin, a novel growth-hormone releasing peptide, was originally isolated from rat and human stomach. Immunohistochemical analyses revealed that ghrelin-immunoreactive neurons were localized in the hypothalamic arcuate nucleus. The function of the digestive organs is controlled from the central nervous system, and the vagus nerve plays an important role. Intracerebroventricular and intravenous administration of ghrelin significantly increased gastric acid secretion, and its effect was abolished by vagotomy. In the present study, the effect of centrally injected ghrelin on pancreatic exocrine secretion was examined in conscious rats. Moreover, an electrophysiologic study was conducted in anesthetized rats to examine whether the excitation of vagal efferent nerve could be induced by ghrelin. To determine the pancreatic exocrine secretion, rats were prepared with cannulae draining bile and pancreatic juice separately. The experiments were conducted in conscious rats on day 4 or 5 after the operation. To exclude the involvement of gastric acid, a proton pump inhibitor omeprazole (5 micromol/kg) was administered into the duodenum 1 h before ghrelin injection. An intracerebroventricular administration of ghrelin (12, 60, and 300 pmol/10 microl) significantly increased pancreatic fluid and protein output in a dose-dependent manner. Pretreatment with the ganglion blocker hexamethonium and with atropine completely abolished the stimulatory effect of central ghrelin. In contrast, an intravenous injection of ghrelin (300 pmol/10 microl) had no effect. Centrally administered ghrelin stimulated the vagal efferent nerve in anesthetized rats. In conclusion, centrally administered ghrelin stimulates pancreatic exocrine secretion through the vagal efferent nerve, and the stimulatory action is independent of gastric acid secretion.