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

Background and Aims: 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-HT₃ and 5-HT₂ 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-HT₃ 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-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 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-HT₃ and 5- HT₂ receptors on vagal afferent fibers to mediate luminal factor-stimulated pancreatic secretion.