Serotonin and cholecystokinin synergistically stimulate rat vagal primary afferent neurones

J Physiol. 2004 Sep 1;559(Pt 2):651-62. doi: 10.1113/jphysiol.2004.064816. Epub 2004 Jul 2.

Abstract

Recent studies indicate that cholecystokinin (CCK) and serotonin (5-hydroxytryptamine, 5-HT) act via vagal afferent fibres to mediate gastrointestinal functions. In the present study, we characterized the interaction between CCK and 5-HT in the vagal primary afferent neurones. Single neuronal discharges of vagal primary afferent neurones innervating the duodenum were recorded from rat nodose ganglia. Two groups of nodose ganglia neurones were identified: group A neurones responded to intra-arterial injection of low doses of cholecystokinin octapeptide (CCK-8; 10-60 pmol); group B neurones responded only to high doses of CCK-8 (120-240 pmol), and were also activated by duodenal distention. CCK-JMV-180, which acts as an agonist in high-affinity states and as an antagonist in low-affinity states, dose dependently stimulated group A neurones, but inhibited the effect of the high doses of CCK-8 on group B neurones. Duodenal perfusion of 5-HT evoked dose-dependent increases in nodose neuronal discharges. Some neurones that responded to 5-HT showed no response to either high or low doses of CCK-8. A separate group of nodose neurones that possessed high-affinity CCK type A (CCK-A) receptors also responded to luminal infusion of 5-HT. Further, a subthreshold dose of CCK-8 (i.e. 5 pmol) produced no measurable electrophysiological effects but it augmented the neuronal responses to 5-HT. This potentiation effect of CCK-8 was eliminated by CR 1409. From these results we concluded that the vagal nodose ganglion contains neurones that may possess only high- or low-affinity CCK-A receptors or 5-HT3 receptors. Some neurones that express high-affinity CCK-A receptors also express 5-HT3 receptors. Pre-exposure to luminal 5-HT may augment the subsequent response to a subthreshold dose of CCK.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • Action Potentials / drug effects*
  • Action Potentials / physiology
  • Animals
  • Cholecystokinin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Neurons, Afferent / drug effects*
  • Neurons, Afferent / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / pharmacology*
  • Vagus Nerve / drug effects*
  • Vagus Nerve / physiology

Substances

  • Serotonin
  • Cholecystokinin