title: Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists.
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-HT(3) 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-HT(3) 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 afferent-mediated 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.
authors.affiliation: Institute of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Lin
authors.forename: You Shuei
authors.initials: YS
authors.lastname: Lin
authors.forename: Ching Jung
authors.initials: CJ
authors.lastname: Lai
authors.forename: Zung Fan
authors.initials: ZF
authors.lastname: Yuan
authors.forename: Ting
authors.initials: T
authors.lastname: Ruan
authors.forename: Yu Ru
authors.initials: YR
authors.lastname: Kou
mesh_terms: D000818:Animals; D001049:Apnea / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D002211:Capsaicin / Q000378:metabolism; D005263:Femoral Artery / Q000187:drug effects / Q000502:physiology; D005268:Femoral Vein / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D058910:Purinergic P2 Receptor Agonists / Q000494:pharmacology; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058469:Receptors, Purinergic P2X / Q000378:metabolism; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
chemical_list: D058910:Purinergic P2 Receptor Agonists; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D002211:Capsaicin