Ethanol causes inflammation in the airways by a neurogenic and TRPV1-dependent mechanism.
Ethanol (EtOH) stimulates peptidergic primary sensory neurons via the activation of the transient receptor potential vanilloid-1 (TRPV1). EtOH is also known to trigger attacks of asthma in susceptible individuals. Our aim was to investigate whether EtOH produces airway inflammation via a TRPV1-dependent mechanism and to verify whether this effect is produced via a mechanism distinct from that of acetaldehyde (AcH). EtOH caused a Ca(2+)-dependent release of neuropeptides from guinea pigs airways, an effect that was inhibited by both capsaicin pretreatment and the TRPV1 antagonist capsazepine (CPZ). Furthermore, EtOH contracted isolated guinea pig bronchi, showing efficacy similar to that of carbachol: this effect of EtOH was sensitive to capsaicin pretreatment, tachykinin receptor blockade, and TRPV1 antagonism. The EtOH metabolite AcH also contracted isolated guinea pig bronchi, but this action was not affected by capsaicin pretreatment, tachykinin receptor, or TRPV1 antagonism. EtOH by intravenous or intragastric route of administration caused bronchoconstriction and increased plasma extravasation in the guinea pig airways, effects that were abolished selectively by CPZ. In conclusion, we have demonstrated that EtOH stimulates peptidergic primary sensory neurons in the guinea pig airways by TRPV1 activation. This excitatory effect of EtOH, distinct from that of AcH, results in neurogenic inflammatory responses that may contribute to the mechanism of EtOH-induced asthma.
Trevisani
Marcello
M
Center of Excellence for the Study of Inflammation, University of Ferrara, 44100 Ferrara, Italy.
Gazzieri
David
D
Benvenuti
Francesca
F
Campi
Barbara
B
Dinh
Q Thai
QT
Groneberg
David A
DA
Rigoni
Michela
M
Emonds-Alt
Xavier
X
Creminon
Christophe
C
Fischer
Axel
A
Geppetti
Pierangelo
P
Harrison
Selena
S
D000079:Acetaldehyde / Q000009:adverse effects; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D001991:Bronchitis / Q000139:chemically induced* / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000009:adverse effects; D002217:Carbachol / Q000009:adverse effects; D000431:Ethanol / Q000009:adverse effects*; D006168:Guinea Pigs; D008297:Male; D011955:Receptors, Drug / Q000502:physiology*; D013373:Substance P / Q000009:adverse effects / Q000378:metabolism
D001798:Blood Proteins; D011955:Receptors, Drug; D013373:Substance P; D000431:Ethanol; D002217:Carbachol; D000079:Acetaldehyde; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin