Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists

Yu Jung Lin, You Shuei Lin, Ching Jung Lai, Zung Fan Yuan, Ting Ruan, Yu Ru Kou

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT3 receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,β-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate- 6-azophenyl-2=,5=- disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT3 receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferentmediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

Original languageEnglish
Pages (from-to)361-370
Number of pages10
JournalJournal of Applied Physiology
Volume114
Issue number3
DOIs
Publication statusPublished - Feb 1 2013

Keywords

  • 5-HT3 receptors
  • Lung
  • P2X receptors
  • Perivagal antagonist treatment
  • Reflex
  • TRPV1
  • Vagal C fibers

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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