Effect of 5-hydroxytryptamine on vagal C-fiber subtypes in guinea pig lungs.
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.
Chuaychoo
Benjamas
B
Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD, USA.
Lee
Min-Goo
MG
Kollarik
Marian
M
Undem
Bradley J
BJ
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000502:physiology; D009620:Nodose Ganglion / Q000166:cytology / Q000502:physiology; D017294:Ondansetron / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology*; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology / Q000502:physiology*
D018490:Serotonin Agents; D012702:Serotonin Antagonists; D012701:Serotonin; D017294:Ondansetron; C045918:2-methyl-5-HT