Hydrogen sulfide causes vanilloid receptor 1-mediated neurogenic inflammation in the airways.
Hydrogen sulfide (H(2)S) is described as a mediator of diverse biological effects, and is known to produce irritation and injury in the lung following inhalation. Recently, H(2)S has been found to cause contraction in the rat urinary bladder via a neurogenic mechanism. Here, we studied whether sodium hydrogen sulfide (NaHS), used as donor of H(2)S, produces responses mediated by sensory nerve activation in the guinea-pig airways. NaHS evoked an increase in neuropeptide release in the airways that was significantly attenuated by capsaicin desensitization and by the transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine. In addition, NaHS caused an atropine-resistant contraction of isolated airways, which was completely prevented by capsaicin desensitization. Furthermore, NaHS-induced contraction was reduced by TRPV1 antagonism (ruthenium red, capsazepine and SB366791), and was abolished by pretreatment with the combination of tachykinin NK(1) (SR140333) and NK(2) (SR48968) receptor antagonists. In anesthetized guinea-pigs, intratracheal instillation of NaHS increased the total lung resistance and airway plasma protein extravasation. These two effects were reduced by TRPV1 antagonism (capsazepine) and tachykinin receptors (SR140333 and SR48968) blockade. Our results provide the first pharmacological evidence that H(2)S provokes tachykinin-mediated neurogenic inflammatory responses in guinea-pig airways, and that this effect is mediated by stimulation of TRPV1 receptors on sensory nerves endings. This novel mechanism may contribute to the irritative action of H(2)S in the respiratory system.
Trevisani
Marcello
M
Center of Excellence for the Study of Inflammation, University of Ferrara, Ferrara, Italy.
Patacchini
Riccardo
R
Nicoletti
Paola
P
Gatti
Raffaele
R
Gazzieri
David
D
Lissi
Nicola
N
Zagli
Giovanni
G
Creminon
Christophe
C
Geppetti
Pierangelo
P
Harrison
Selena
S
D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D009924:Organ Culture Techniques; D018039:Receptors, Tachykinin / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013990:Tidal Volume / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000378:metabolism
D009479:Neuropeptides; D018039:Receptors, Tachykinin; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D006862:Hydrogen Sulfide