title: Serotonin released from intestinal enterochromaffin cells mediates luminal non-cholecystokinin-stimulated pancreatic secretion in rats.
abstract: OBJECTIVE
  Similar to cholecystokinin (CCK), non-CCK-dependent duodenal factors stimulate vagal mucosal afferent fibers to mediate pancreatic enzyme secretion via a common cholinergic pathway. We tested the hypothesis that 5-hydroxytryptamine (5-HT) released from enterochromaffin (EC) cells plays an important role in the transduction of luminal information to the central nervous system via vagal afferent fibers to mediate pancreatic secretion.
  
  
  METHODS
  Pancreatic secretions were examined in conscious rats after intragastric administration of chopped rodent chow in the presence and absence of CCK or 5-HT(3) and 5-HT(2) antagonists. Pancreatic responses to intraduodenal administration of maltose, hyperosmolar NaCl, and light mucosal stroking were examined in rats pretreated with various pharmacological antagonists or after surgical or chemical ablation of vagal and 5-HT neural pathways.
  
  
  RESULTS
  Administration of L364, 718 inhibited 54% of pancreatic protein secretion evoked by intragastric administration of rodent chow. L364,714 and ICS 205-930, a 5-HT(3) antagonist, combined produced a 94% inhibition. Vagal afferent rootlet section eliminated pancreatic secretions evoked by intraduodenal stimuli. p-Chlorophenylalanine, a 5-HT synthesis inhibitor, but not 5,7-hydroxytryptamine, a 5-HT neurotoxin, also eliminated the pancreatic response to these luminal stimuli. The 5-HT(3) antagonist markedly inhibited pancreatic secretion induced by maltose and hyperosmolar NaCl. 5-HT(2) and 5-HT(3) antagonists combined inhibited the pancreatic response to light stroking of the mucosa.
  
  
  CONCLUSIONS
  Luminal factors such as osmolality, disaccharides, and mechanical stimulation stimulated pancreatic secretion via intestinal vagal mucosal afferent fibers. It is likely that 5-HT originating from intestinal EC cells activated 5-HT(3) and 5-HT(2) receptors on vagal afferent fibers to mediate luminal factor-stimulated pancreatic secretion.
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Hao
authors.forename: J
authors.initials: J
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Owyang
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D003243:Consciousness; D020109:Devazepide / Q000494:pharmacology; D004386:Duodenum / Q000502:physiology; D004435:Eating; D004750:Enteral Nutrition; D004759:Enterochromaffin Cells / Q000378:metabolism*; D010134:Fenclonine / Q000494:pharmacology; D005753:Gastric Mucosa / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D006982:Hypertonic Solutions / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008320:Maltose / Q000494:pharmacology; D009412:Nerve Fibers / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D010179:Pancreas / Q000294:innervation / Q000378:metabolism*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D000077526:Tropisetron
chemical_list: D006727:Hormone Antagonists; D006982:Hypertonic Solutions; D007211:Indoles; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D044406:Receptors, Serotonin, 5-HT3; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017673:Sodium Chloride, Dietary; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D008320:Maltose; D000077526:Tropisetron; D002766:Cholecystokinin; D020109:Devazepide; D010134:Fenclonine