Central Orexin-A stimulates pancreatic exocrine secretion via the vagus

Digestive organs are controlled from the central nervous system, and the vagus nerve plays an important role. Orexins are recently purified neuropeptides localized in neurons within the lateral hypothalamus. To examine the effects of centrally injected Orexin-A and B on pancreatic exocrine secretion in conscious rats. Rats were prepared with cannulae draining bile and pancreatic juice separately. The experiments were conducted without anesthesia on day 4 or 5 after the operation. Intracerebroventricular administration of Orexin-A (0.25, 0.5, and 1.0 nmol) significantly increased pancreatic fluid and protein output in a dose-dependent manner. A significant stimulatory effect of Orexin-B was not observed. Pretreatment with the ganglion blocker hexamethonium and with atropine completely abolished the stimulatory effect of central Orexin-A. Central Orexin-A significantly increased pancreatic secretion after pretreatment with omeprazole. Intravenous injection of Orexin-A had no effect. Centrally administered Orexin-A stimulated the vagal efferent nerve in anesthetized rats. Centrally administered Orexin-A stimulates pancreatic exocrine secretion through the vagal efferent nerve, and the stimulatory action is independent of gastric acid secretion.