title: A synergistic effect of simultaneous TRPA1 and TRPV1 activations on vagal pulmonary C-fiber afferents.
abstract: Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are coexpressed in vagal pulmonary C-fiber sensory nerves. Because both these receptors are sensitive to a number of endogenous inflammatory mediators, it is conceivable that they can be activated simultaneously during airway inflammation. This study aimed to determine whether there is an interaction between these two polymodal transducers upon simultaneous activation, and how it modulates the activity of vagal pulmonary C-fiber sensory nerves. In anesthetized, spontaneously breathing rats, the reflex-mediated apneic response to intravenous injection of a combined dose of allyl isothiocyanate (AITC, a TRPA1 activator) and capsaicin (Cap, a TRPV1 activator) was ∼202% greater than the mathematical sum of the responses to AITC and Cap when they were administered individually. Similar results were also observed in anesthetized mice. In addition, the synergistic effect was clearly demonstrated when the afferent activity of single vagal pulmonary C-fiber afferents were recorded in anesthetized, artificially ventilated rats; C-fiber responses to AITC, Cap and AITC + Cap (in combination) were 0.6 ± 0.1, 0.8 ± 0.1, and 4.8 ± 0.6 impulses/s (n = 24), respectively. This synergism was absent when either AITC or Cap was replaced by other chemical activators of pulmonary C-fiber afferents. The pronounced potentiating effect was further demonstrated in isolated vagal pulmonary sensory neurons using the Ca(2+) imaging technique. In summary, this study showed a distinct positive interaction between TRPA1 and TRPV1 when they were activated simultaneously in pulmonary C-fiber sensory nerves.
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky;
authors.forename: Yu-Jung
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky;
authors.forename: Ruei-Lung
authors.initials: RL
authors.lastname: Lin
authors.affiliation: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; and.
authors.forename: Ting
authors.initials: T
authors.lastname: Ruan
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Kentucky Medical Center, Lexington, Kentucky.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khosravi
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, Kentucky; lylee@uky.edu.
authors.forename: Lu-Yuan
authors.initials: LY
authors.lastname: Lee
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D017879:Isothiocyanates / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D050916:TRPV Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
chemical_list: D017879:Isothiocyanates; D050916:TRPV Cation Channels; D050051:Transient Receptor Potential Channels; C004471:allyl isothiocyanate; D002211:Capsaicin
keywords: AITC; TRPA1; TRPV1; capsaicin; inflammation