Central Orexin-A Stimulates Pancreatic Exocrine Secretion via the Vagus

Introduction 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. Aim To examine the effects of centrally injected Orexin-A and B on pancreatic exocrine secretion in conscious rats. Methodology 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. Results 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. Conclusions Centrally administered Orexin-A stimulates pancreatic exocrine secretion through the vagal efferent nerve, and the stimulatory action is independent of gastric acid secretion.

[1]  A. Kirchgessner,et al.  Orexin Synthesis and Response in the Gut , 1999, Neuron.

[2]  M. G. Dube,et al.  Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action 1 This study was presented in part at the 28th Annual Meeting of the Society for Neuroscience, Los Angeles, CA, in November 1998. 1 , 1999, Brain Research.

[3]  D. Grundy,et al.  Plasticity in the mesenteric afferent response to cisplatin following vagotomy in the rat. , 1999, Journal of the autonomic nervous system.

[4]  T. Okumura,et al.  Stimulation of gastric acid secretion by centrally administered orexin-A in conscious rats. , 1999, Biochemical and biophysical research communications.

[5]  T. Sakurai,et al.  Orexins, orexigenic hypothalamic peptides, interact with autonomic, neuroendocrine and neuroregulatory systems. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Carr,et al.  Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior , 1998, Cell.

[7]  F E Bloom,et al.  The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Carr,et al.  Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. , 1998, Cell.

[9]  S. Kanai,et al.  Inhibitory effect of central dopamine on basal pancreatic secretion in conscious rats. , 1998, American journal of physiology. Gastrointestinal and liver physiology.

[10]  Yang Wang,et al.  Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats. , 1997, The American journal of physiology.

[11]  T. Lundeberg,et al.  Interleukin-1β sensitizes the response of the gastric vagal afferent to cholecystokinin in rat , 1997, Neuroscience Letters.

[12]  K. Miyasaka,et al.  Central somatostatin prevents vagal efferent nerve excitation produced by TRH but not by 2-deoxy-D-glucose. , 1997, The American journal of physiology.

[13]  T. Lundeberg,et al.  Interleukin-1 increases activity of the gastric vagal afferent nerve partly via stimulation of type A CCK receptor in anesthetized rats. , 1997, Journal of the autonomic nervous system.

[14]  A. Funakoshi,et al.  Somatostatin inhibits pancreatic exocrine secretion centrally via sympathetic nerves in conscious rats. , 1995, Journal of the autonomic nervous system.

[15]  T. Okumura,et al.  Microinjection of TRH analogue into the dorsal vagal complex stimulates pancreatic secretion in rats. , 1995, The American journal of physiology.

[16]  T. Okumura,et al.  Pancreatic polypeptide microinjection into the dorsal motor nucleus inhibits pancreatic secretion in rats. , 1995, Gastroenterology.

[17]  D. McTigue,et al.  Vagovagal reflex control of digestion: afferent modulation by neural and "endoneurocrine" factors. , 1995, The American journal of physiology.

[18]  S. Mulvihill,et al.  Vagal stimulation of rat exocrine pancreatic secretion occurs via multiple mediators. , 1993, Gastroenterology.

[19]  C. Owyang,et al.  Vagal afferent pathway mediates physiological action of cholecystokinin on pancreatic enzyme secretion. , 1993, The Journal of clinical investigation.

[20]  H. Tamamura,et al.  Inhibitory effect of pancreastatin on pancreatic exocrine secretions. Pancreastatin inhibits central vagal nerve stimulation. , 1990, Gastroenterology.

[21]  Y. Taché,et al.  Brain Regulation of Gastric Acid Secretion by Peptides , 1990, Annals of the New York Academy of Sciences.

[22]  G. Green.  Role of Gastric Juice in Feedback Regulation of Rat Pancreatic Secretion by Luminal Proteases , 1990, Pancreas.

[23]  G. Green,et al.  The Sequential Changes in Pancreatic Exocrine Function After Abdominal Surgery in the Rat , 1986, Pancreas.

[24]  Y. Oomura,et al.  Effects of hypothalamic lesion on pancreatic autonomic nerve activity in the rat , 1984, Brain Research.

[25]  W. Oldendorf,et al.  Influence of cisternal pressure on passage of neuropeptides from the cerebrospinal fluid into the peripheral circulation , 1984, Brain Research.

[26]  T. Kanno,et al.  Thyrotropin-releasing hormone injected intracerebroventricularly in the rat stimulates exocrine pancreatic secretion via the vagus nerve , 1983, Regulatory Peptides.

[27]  G. Green,et al.  Effect of Atropine on Rat Basal Pancreatic Secretion during Return or Diversion of Bile-Pancreatic Juice , 1983, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[28]  S. Sjöstrand,et al.  Inhibition of gastric acid secretion by omeprazole in the dog and rat. , 1983, Gastroenterology.

[29]  W. Oldendorf,et al.  Rapid appearance of intraventricularly administered neuropeptides in the peripheral circulation , 1982, Brain Research.

[30]  P. J. Keller,et al.  The proteins of bovine pancreatic juice. , 1958, The Journal of biological chemistry.