Interaction between TRPA1 and TRPV1: Synergy on pulmonary sensory nerves.
Transient receptor potential ankyrin type 1 (TRPA1) and vanilloid type 1 (TRPV1) receptors are co-expressed in vagal pulmonary C-fiber sensory nerves. Because both these ligand-gated non-selective cation channels are sensitive to a number of endogenous inflammatory mediators, it is highly probable that they can be activated simultaneously during airway inflammation. Studies were carried out to investigate 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. Our studies showed a distinct potentiating effect induced abruptly by simultaneous activations of TRPA1 and TRPV1 by their respective selective agonists, allyl isothiocyanate (AITC) and capsaicin (Cap), at near-threshold concentrations. This synergistic effect was demonstrated in the studies of single-unit recording of vagal bronchopulmonary C-fiber afferents and the reflex responses elicited by activation of these afferents in intact animals, as well as in the isolated nodose and jugular bronchopulmonary sensory neurons. This potentiating effect was absent when either AITC or Cap was replaced by non-TRPA1 and non-TRPV1 chemical activators of these neurons, demonstrating the selectivity of the interaction between these two TRP channels. Furthermore, the synergism was dependent upon the extracellular Ca(2+), and the rapid onset of the action further suggests that the interaction probably occurred locally at the sites of these channels. These findings suggest that the TRPA1-TRPV1 interaction may play an important role in regulating the function and excitability of pulmonary sensory neurons during airway inflammation, but the mechanism underlying this positive interaction is not yet fully understood.
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA. Electronic address: lylee@uky.edu.
Lu-Yuan
LY
Lee
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Chun-Chun
CC
Hsu
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Yu-Jung
YJ
Lin
Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Ruei-Lung
RL
Lin
Department of Internal Medicine, University of Kentucky Medical Center, Lexington, KY 40536-0298, USA.
Mehdi
M
Khosravi
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000294:innervation*; D036421:Nerve Fibers, Unmyelinated; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D011014:Pneumonia / Q000503:physiopathology; D011984:Sensory Receptor Cells / Q000502:physiology*; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000235:genetics* / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000502:physiology*
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D050051:Transient Receptor Potential Channels
Airway; C fiber; Inflammation; TRPA1; TRPV1