Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs

Pulm Pharmacol Ther. 2005;18(4):269-76. doi: 10.1016/j.pupt.2004.12.010.


5-Hydroxytryptamine (5-HT, serotonin) evokes pulmonary reflexes partially by activating vagal bronchopulmonary C-fibers. In the guinea pig, vagal bronchopulmonary C-fibers arise from cell bodies situated in the nodose and the jugular ganglia. The nodose and the jugular C-fibers differ both pharmacologically and neurochemically, and may subserve different functions. In this study, we compared the effect of 5-HT on the nodose and jugular C-fibers with receptive fields within the guinea pig lungs. The nerve terminals of the vagal bronchopulmonary C-fibers were studied in an ex vivo isolated perfused lung nerve preparation using the extracellular recordings. All nodose C-fibers responded to transient administration of 5-HT (10 microM) and to the selective 5-HT3 receptor agonist, 2-methyl-5-HT (10 microM), with the action potential discharge. The selective 5-HT3 receptor antagonist ondansetron (10 microM) inhibited (by approximately 90%) the activation of the nodose C-fibers evoked by 5-HT (10 microM). In contrast to the nodose C-fibers, the jugular C-fibers were unresponsive or poorly responsive to 5-HT (n=9) and unresponsive to 2-methyl-5-HT (n=11). A direct action of 5-HT on the C-fiber neurons was supported using the whole cell patch clamp recordings from the isolated vagal sensory neurons retrogradely labeled from the lungs. Consistently with the studies on the nerve terminals, 5-HT (10 microM) induced inward current in nodose lung-specific capsaicin-sensitive neurons. Conversely, 5-HT was inefficient to stimulate the lung-specific jugular neurons. We conclude that in the guinea pig lungs, 5-HT selectively stimulates vagal nodose, but not jugular C-fibers via the 5-HT3 receptors in the neuronal membrane.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Guinea Pigs
  • Lung / drug effects*
  • Lung / innervation
  • Lung / physiology
  • Male
  • Membrane Potentials / drug effects
  • Nerve Fibers, Unmyelinated / drug effects*
  • Nerve Fibers, Unmyelinated / physiology
  • Nodose Ganglion / cytology
  • Nodose Ganglion / physiology
  • Ondansetron / pharmacology
  • Patch-Clamp Techniques / methods
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology*
  • Serotonin Agents / pharmacology
  • Serotonin Antagonists / pharmacology
  • Vagus Nerve / cytology
  • Vagus Nerve / physiology*


  • Serotonin Agents
  • Serotonin Antagonists
  • Serotonin
  • Ondansetron
  • 2-methyl-5-HT