title: Pharmacology of Bradykinin-Evoked Coughing in Guinea Pigs.
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 N(G)-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.
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.).
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hewitt
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.).
authors.forename: Gregory
authors.initials: G
authors.lastname: Adams
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.).
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Mazzone
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.).
authors.forename: Nanako
authors.initials: N
authors.lastname: Mori
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.).
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: The Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland (G.A., N.M., B.J.C.); University of Pennsylvania, Philadelphia, Pennsylvania (M.M.H.); University of Queensland, Australia (S.B.M.); and Department of Respiratory Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai, China (L.Y.) bjc@jhmi.edu.
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Canning
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D001986:Bronchial Spasm / Q000150:complications; D003371:Cough / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000378:metabolism
chemical_list: D043782:Receptor, Bradykinin B2; D010447:Peptide Hydrolases; D001920:Bradykinin