Intestinal serotonin acts as a paracrine substance to mediate vagal signal transmission evoked by luminal factors in the rat

J Physiol. 2001 Feb 1;530(Pt 3):431-42. doi: 10.1111/j.1469-7793.2001.0431k.x.

Abstract

The vagus nerve conveys primary afferent information produced by a meal to the brainstem. Serotonin (5-HT), which abounds in intestinal enterochromaffin cells, is released in response to various stimuli. We have recently demonstrated that 5-HT released from intestinal enterochromaffin cells activates 5-HT3 receptors on vagal afferent fibres to mediate luminal non-cholecystokinin-stimulated pancreatic secretion. The present study was designed to evaluate the responses of vagal sensory neurons to intraluminal osmotic stimulation and luminal infusion of maltose, glucose or 5-HT. We investigated the role of endogenous 5-HT in signal transmission evoked by luminal stimuli to activate vagal sensory neurons. The discharges of vagal primary afferent neurons innervating the intestine were recorded from rat nodose ganglia. Luminal factors such as intestinal osmotic stimuli and perfusion of carbohydrates elicited powerful vagal nodose responses. Electrical subdiaphragmatic vagal stimulation activated 364 single units; 40 of these responded to intestinal mucosal stimuli. Of these 40, 30 responded to intraduodenal perfusion of hyperosmolar NaCl (500 mosmol l(-1)), 27 responded to tap water (5 mosmol l(-1)) and 20 and 19 responded to maltose (300 mM) and glucose (277.5 mM), respectively. The 5-HT3/4 antagonist tropisetron (ICS 205-930) or 5-HT3 antagonist granisetron abolished luminal stimuli-evoked nodose neuronal responses. Intraluminal infusion of 10(-5) and 10(-4) M 5-HT elicited increases in vagal afferent discharge in 25 and 31 units, respectively, by activating the 5-HT3 receptors. Acute subdiaphragmatic vagotomy, intestinal mucosal application of the local anaesthetic lidocaine (lignocaine) or administration of 5-HT3 antagonist each abolished the luminal 5-HT-induced nodose neuronal responses. In contrast, distension-sensitive neurons did not respond to duodenal infusion of 5-HT. Pharmacological depletion of 5-HT stores using p-chlorophenylalanine (PCPA), a 5-HT-synthesis inhibitor, abolished luminal factor-stimulated nodose neuronal responses. In contrast, pretreatment with 5,7-dihydroxytryptamine (5,7-DHT), a specific 5-HT neurotoxin that destroys 5-HT-containing neurons without affecting 5-HT-containing mucosal cells, had no effect on these responses. These results suggested that the nodose neuronal responses to luminal osmolarity and to the digestion products of carbohydrates are dependent on the release of endogenous 5-HT from the mucosal enterochromaffin cells, which acts on the 5-HT3 receptors on vagal afferent fibres to stimulate vagal sensory neurons.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Anesthetics, Local / pharmacology
  • Animals
  • Brain Stem / physiology
  • Cholecystokinin / pharmacology
  • Duodenum / innervation
  • Granisetron / pharmacology
  • Intestinal Mucosa / innervation
  • Intestinal Mucosa / physiology
  • Intestines / innervation*
  • Ketanserin / pharmacology
  • Lidocaine / pharmacology
  • Male
  • Muscle, Smooth / innervation
  • Nerve Fibers / physiology
  • Neurons, Afferent / drug effects
  • Neurons, Afferent / physiology
  • Nodose Ganglion / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / pharmacology
  • Serotonin / physiology*
  • Vagotomy
  • Vagus Nerve / drug effects
  • Vagus Nerve / physiology*

Substances

  • Anesthetics, Local
  • Serotonin
  • Cholecystokinin
  • Ketanserin
  • Lidocaine
  • Granisetron