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Bradykinin sensitizes the cough reflex via a B(2) receptor dependent activation of TRPV1 and TRPA1 channels through metabolites of cyclooxygenase and 12-lipoxygenase
BACKGROUND: Inhaled bradykinin (BK) has been reported to both sensitize and induce cough but whether BK can centrally sensitize the cough reflex is not fully established. In this study, using a conscious guinea-pig model of cough, we investigated the role of BK in the central sensitization of the co...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6551914/ https://www.ncbi.nlm.nih.gov/pubmed/31170972 http://dx.doi.org/10.1186/s12931-019-1060-8 |
Sumario: | BACKGROUND: Inhaled bradykinin (BK) has been reported to both sensitize and induce cough but whether BK can centrally sensitize the cough reflex is not fully established. In this study, using a conscious guinea-pig model of cough, we investigated the role of BK in the central sensitization of the cough reflex and in airway obstruction. METHODS: Drugs were administered, to guinea pigs, by the intracerebroventricular (i.c.v.) route. Aerosolized citric acid (0.2 M) was used to induce cough in a whole-body plethysmograph box, following i.c.v. infusion of drugs. An automated analyser recorded both cough and airway obstruction simultaneously. RESULTS: BK, administered by the i.c.v. route, dose-dependently enhanced the citric acid-induced cough and airway obstruction. This effect was inhibited following i.c.v. pretreatment with a B(2) receptor antagonist, TRPV1 and TRPA1 channels antagonists and cyclooxygenase (COX) and 12-lipoxygenase (12-LOX) inhibitors. Furthermore, co-administration of submaximal doses of the TRPV1 and TRPA1 antagonists or the COX and 12-LOX inhibitors resulted in a greater inhibition of both cough reflex and airway obstruction. CONCLUSIONS: Our findings show that central BK administration sensitizes cough and enhances airway obstruction via a B(2) receptor/TRPV1 and/or TRPA1 channels which are coupled via metabolites of COX and/or 12-LOX enzymes. In addition, combined blockade of TRPV1 and TRPA1 or COX and 12-LOX resulted in a greater inhibitory effect of both cough and airway obstruction. These results indicate that central B(2) receptors, TRPV1/TRPA1 channels and COX/12-LOX enzymes may represent potential therapeutic targets for the treatment of cough hypersensitivity. GRAPHICAL ABSTRACT: [Image: see text] |
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