Pharmacology of bradykinin-evoked coughing in guinea pigs

Hewitt, Matthew M., Adams, Gregory, Jr., Mazzone, Stuart B., Mori, Nanako, Yu, Li and Canning, Brendan J. (2016) Pharmacology of bradykinin-evoked coughing in guinea pigs. Journal of Pharmacology and Experimental Therapeutics, 357 3: 620-628. doi:10.1124/jpet.115.230383

Author Hewitt, Matthew M.
Adams, Gregory, Jr.
Mazzone, Stuart B.
Mori, Nanako
Yu, Li
Canning, Brendan J.
Title Pharmacology of bradykinin-evoked coughing in guinea pigs
Journal name Journal of Pharmacology and Experimental Therapeutics   Check publisher's open access policy
ISSN 1521-0103
Publication date 2016-03-21
Year available 2016
Sub-type Article (original research)
DOI 10.1124/jpet.115.230383
Open Access Status Not Open Access
Volume 357
Issue 3
Start page 620
End page 628
Total pages 9
Place of publication Bethesda, MD,United States
Publisher American Society for Pharmacology and Experimental Therapy
Collection year 2017
Language eng
Formatted abstract
Bradykinin has been implicated as a mediator of the acute pathophysiological and inflammatory consequences of respiratory tract infections and in exacerbations of chronic diseases such as asthma. Bradykinin may also be a trigger for the coughing associated with these and other conditions. We have thus set out to evaluate the pharmacology of bradykinin-evoked coughing in guinea pigs. When inhaled, bradykinin induced paroxysmal coughing that was abolished by the bradykinin B2 receptor antagonist HOE 140. These cough responses rapidly desensitized, consistent with reports of B2 receptor desensitization. Bradykinin-evoked cough was potentiated by inhibition of both neutral endopeptidase and angiotensin-converting enzyme (with thiorphan and captopril, respectively), but was largely unaffected by muscarinic or thromboxane receptor blockade (atropine and ICI 192605), cyclooxygenase, or nitric oxide synthase inhibition (meclofenamic acid and NG-nitro-L-arginine). Calcium influx studies in bronchopulmonary vagal afferent neurons dissociated from vagal sensory ganglia indicated that the tachykinin-containing C-fibers arising from the jugular ganglia mediate bradykinin-evoked coughing. Also implicating the jugular C-fibers was the observation that simultaneous blockade of neurokinin2 (NK2; SR48968) and NK3 (SR142801 or SB223412) receptors nearly abolished the bradykinin-evoked cough responses. The data suggest that bradykinin induces coughing in guinea pigs by activating B2 receptors on bronchopulmonary C-fibers. We speculate that therapeutics targeting the actions of bradykinin may prove useful in the treatment of cough.
Keyword Angiotensin-converting enzyme
Pulmonary inflation pressure
Rapidly adapting receptor
Bradykin-evoked coughing
Inflammatory response
Respiratory tract infection
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Biomedical Sciences Publications
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