title: Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors.
abstract: We recently demonstrated that luminal factors such as osmolality, disaccharides, and mechanical stimulation evoke pancreatic secretion by activating 5-hydroxytryptamine subtype 3 (serotonin-3, 5-HT3) receptors on mucosal vagal afferent fibers in the intestine. We hypothesized that 5-HT released by luminal stimuli acts as a paracrine substance, activating the mucosal vagal afferent fibers to stimulate pancreatic secretion. In the in vivo rat model, luminal perfusion of maltose or hypertonic NaCl increased 5-HT level threefold in intestinal effluent perfusates. Similar levels were observed after intraluminal 10(-5) M 5-HT perfusion. These treatments did not affect 5-HT blood levels. In a separate study, intraduodenal, but not intraileal, 5-HT application induced a dose-dependent increase in pancreatic protein secretion, which was not blocked by the CCK-A antagonist CR-1409. Acute vagotomy, methscopolamine, or perivagal or intestinal mucosal application of capsaicin abolished 5-HT-induced pancreatic secretion. In conscious rats, luminal 10(-5) M 5-HT administration produced a 90% increase in pancreatic protein output, which was markedly inhibited by the 5-HT3 antagonist ondansetron. In conclusion, luminal stimuli induce 5-HT release, which in turn activates 5-HT3 receptors on mucosal vagal afferent terminals. In this manner, 5-HT acts as a paracrine substance to stimulate pancreatic secretion via a vagal cholinergic pathway.
authors.affiliation: Gastroenterology Research Unit, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan 48109-0682, USA. yli@umich.edu
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: X Y
authors.initials: XY
authors.lastname: Wu
authors.forename: J X
authors.initials: JX
authors.lastname: Zhu
authors.forename: C
authors.initials: C
authors.lastname: Owyang
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007421:Intestine, Small / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008320:Maltose / Q000494:pharmacology; D019832:N-Methylscopolamine / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D019899:Paracrine Communication; D010276:Parasympatholytics / Q000494:pharmacology; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3; D012701:Serotonin / Q000008:administration & dosage / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D014628:Vagotomy
chemical_list: D010276:Parasympatholytics; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D012701:Serotonin; D008320:Maltose; D002211:Capsaicin; D019832:N-Methylscopolamine