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Luminal melatonin stimulates pancreatic enzyme secretion via activation of serotonin-dependent nerves
Katarzyna Nawrot-Porąbka1, Jolanta Jaworek, Anna Leja-Szpak
1Department of Medical Physiology, Faculty of Health Sciences, Jagiellonian University School of Medicine, Michałowskiego 12, PL 31-126 Kraków, Poland.
Background:
Serotonin (5-HT) is released from enterochromaffin cells in the gastrointestinal tract. 5-HT, via the activation of 5-HT2 and 5-HT3 receptors on vagal fibers, mediates pancreatic secretion through the mechanism independent from cholecystokinin. Melatonin (5-HT derivative) or L-tryptophan (melatonin or 5-HT precursor) given systemically or intraduodenally to the rats stimulate amylase secretion, but the mechanism is not clear. The aim of this study was to investigate the involvement of 5-HT in the pancreatostimulatory effect of melatonin or L-tryptophan, administered intraduodenally.
Methods:
Wistar rats were surgically equipped with silicone catheters; inserted into pancreato-biliary duct and into the duodenum. Melatonin, L-tryptophan or 5-HT were given to the rats as a bolus. Combination of 5-HT2 or 5-HT3 receptor antagonists: ketanserin (100 μg/kg) and MDL72222 (250 μg/kg) was given intraperitoneally to the animals, 15 min. prior to the administration of the examined substances. The role of the vagal nerve, sensory fibers and CCK in the control of pancreatic exocrine function were determined. Blood samples were taken for the determination of 5-HT.
Results:
Melatonin, 5-HT or L-tryptophan increased pancreatic amylase secretion. The stimulatory effect of the above substances was decreased by pretreatment of the rats with ketanserin and MDL72222. Bilateral vagotomy completely abolished the increase of amylase output caused by 5-HT, while capsaicin deactivation of sensory nerves or blockade of CCK1 receptor only partially reversed the stimulatory effect of 5-HT on the pancreas. Intraduodenal L-tryptophan, but not melatonin, increased plasma 5-HT concentrations in a dose- and time-dependent manner.
Conclusion:
Stimulation of pancreatic exocrine function caused by intraluminal administration of melatonin, or L-tryptophan is modified, at least in part, by serotoninergic mechanisms and vagal nerves.
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