Serotonin released from intestinal enterochromaffin cells mediates luminalnon-cholecystokinin-stimulated pancreatic secretion in rats

Background & Aims: Similar to cholecystokinin (CCK), non-CCK-dependent duod enal factors stimulate vagal mucosal afferent fibers to mediate pancreatic enzyme secretion via a common cholinergic pathway. We tested the hypothesis that Ei-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 secr etion. Methods: Pancreatic secretions were examined in conscious rats after intragastric administration of chopped rodent chow in the presence and abs ence of CCK or 5-HT3 and 5-HT2 antagonists. Pancreatic responses to intradu odenal administration of maltose, hyperosmolar NaCl, and light mucosal stro king were examined in rats pretreated with various pharmacological antagoni sts or after surgical or chemical ablation of vagal and 5-HT neural pathway s. Results: Administration of L364,718 inhibited 54% of pancreatic protein secretion evoked by intragastric administration of rodent chow. L364,714 an d ICS 205-930, a 5-HT3 antagonist, combined produced a 94% inhibition. Vaga l afferent rootlet section eliminated pancreatic secretions evoked by intra duodenal stimuli, p-Chlorophenylalanine, a 5-HT synthesis inhibitor, but no t 5,7-hydroxytryptamine, a 5-HT neurotoxin, also eliminated the pancreatic response to these luminal stimuli. The 5-HT3 antagonist markedly inhibited pancreatic secretion induced by maltose and hyperosmolar NaCl. 5-HT2 and 5- HT3 antagonists combined inhibited the pancreatic response to light strokin g of the mucosa. Conclusions: Luminal factors such as osmolality, disacchar ides, and mechanical stimulation stimulated pancreatic secretion via intest inal vagal mucosal afferent fibers. It is likely that 5-HT originating from intestinal EC cells activated 5-HT3 and 5-HT2 receptors on vagal afferent fibers to mediate luminal factor-stimulated pancreatic secretion.