title: Ethanol potentiates the TRPV1-mediated cough in the guinea pig.
abstract: Ethanol is a chemical irritant able to induce a large variety of effects in the airways. It has been reported that ethanol sensitizes the transient receptor potential vanilloid-1 (TRPV1) to various stimuli and inhalation of ethanol enhances the cough mediated by TRPV1 activation (capsaicin) in patients suffering of airway sensory hyperreactivity. Here, we set out to investigate whether ethanol sensitizes the cough induced by TRPV1 activation in a guinea pig model and the possible mechanism of such exacerbating effect. Aerosolized resiniferatoxin (RTX, 0.5 microM) and hypertonic saline (7%) produced a cough response dependent and independent of TRPV1 activation, respectively. Ethanol (3%, 10 min) inhalation, that per se did not cause any tussive response, significantly increased the number of coughs evoked by RTX inhalation without affecting hypertonic saline (7%) induced cough. Potentiation by ethanol of the tussive response to RTX was prevented by the PKC inhibitor, GF109203X (GFX). In conclusion, ethanol selectively exaggerates, via a PKC-dependent pathway, the cough response evoked by TRPV1 stimulation. The present results may contribute to explain respiratory distresses sometimes associated to alcohol consumption, including cough and asthma.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, 44100 Ferrara, Italy. gttrfl@unife.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Gatti
authors.forename: Eunice
authors.initials: E
authors.lastname: Andre
authors.forename: Campi
authors.initials: C
authors.lastname: Barbara
authors.forename: Thai Q
authors.initials: TQ
authors.lastname: Dinh
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fontana
authors.forename: Axel
authors.initials: A
authors.lastname: Fischer
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Geppetti
authors.forename: Marcello
authors.initials: M
authors.lastname: Trevisani
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D003371:Cough / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000633:toxicity; D000431:Ethanol / Q000633:toxicity*; D006168:Guinea Pigs; D008297:Male; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D012462:Saline Solution, Hypertonic / Q000633:toxicity; D050916:TRPV Cation Channels / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004224:Diterpenes; D012462:Saline Solution, Hypertonic; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D000431:Ethanol; C024353:resiniferatoxin; D011493:Protein Kinase C