Intestinal serotonin acts as paracrine substance to mediate pancreatic secretion stimulated by luminal factors

We recently demonstrated that luminal factors such as osmolality, disacchar ides, and mechanical stimulation evoke pancreatic secretion by activating 5 -hydroxytryptamine subtype 3 (serotonin-3, 5-HT3) receptors on mucosal vaga l afferent fibers in the intestine. We hypothesized that 5-HT released by l uminal 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 thre efold 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 secret ion, which was not blocked by the CCK-A antagonist CR-1409. Acute vagotomy, methscopolamine, or perivagal or intestinal mucosal application of capsaic in 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. I n conclusion, luminal stimuli induce 5-HT release, which in turn activates 5-HT3 receptors on mucosal vagal afferent terminals. In this manner, 5-HT a cts as a paracrine substance to stimulate pancreatic secretion via a vagal cholinergic pathway.