Bradykinin sensitizes the cough reflex via a B2 receptor dependent activation of TRPV1 and TRPA1 channels through metabolites of cyclooxygenase and 12-lipoxygenase

Autor:	Ahmed Z. El-Hashim, Fajer Al-Shamlan
Jazyk:	angličtina
Rok vydání:	2019
Předmět:	0301 basic medicine Cough reflex TRPV1 Bradykinin Pharmacology TRPA1 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Plethysmograph B2 receptors Receptor lcsh:RC705-779 biology business.industry Antagonist food and beverages lcsh:Diseases of the respiratory system Airway obstruction Central sensitization medicine.disease respiratory tract diseases 030104 developmental biology 030228 respiratory system chemistry Cough biology.protein Cyclooxygenase business psychological phenomena and processes
Zdroj:	Respiratory Research, Vol 20, Iss 1, Pp 1-15 (2019)
Popis:	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 B2 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 B2 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 B2 receptors, TRPV1/TRPA1 channels and COX/12-LOX enzymes may represent potential therapeutic targets for the treatment of cough hypersensitivity. Graphical abstract
Databáze:	OpenAIRE
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