{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T14:03:19Z","timestamp":1774620199282,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[1999,2,1]],"date-time":"1999-02-01T00:00:00Z","timestamp":917827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>To further define the role of neural responses in the hyperreactivity of inflamed human upper airways to bradykinin (BK), we determined if repeated challenges with BK led to tachyphylaxis of neurally mediated responses in subjects with perennial allergic rhinitis. We also tested the hypothesis that enhanced reactivity to kinins in inflamed airways was caused by induction of B1-kinin receptors by comparing the effects of the selective B1-receptor agonist, des-Arg10-lysylbradykinin, and the B2 receptor agonist, BK, in the lower airways of asthmatics and in the upper airways of subjects with perennial allergic rhinitis. Repeated BK challenges led to tachyphylaxis of sneezing and of neurally mediated serous glandular secretion in subjects with perennial allergic rhinitis. Surprisingly, tachyphylaxis of increased local vascular permeability was also observed. By contrast, repeated challenges with BK in normal subjects led to reproducible increases in vascular permeability. Provocation with des-Arg10-lysylbradykinin did not cause bronchoconstriction in asthmatic subjects or increase glandular secretion or vascular permeability in the upper airways of subjects with rhinitis. We conclude that increased reactivity to kinins in inflamed human airways is mediated, at least in part, by neural reflexes, and is not caused by induction of B1-receptors.<\/jats:p>","DOI":"10.1164\/ajrccm.159.2.9804132","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:53:04Z","timestamp":1365083584000},"page":"431-438","source":"Crossref","is-referenced-by-count":19,"title":["Airway Neural Responses to Kinins: Tachyphylaxis and Role of Receptor Subtypes"],"prefix":"10.1093","volume":"159","author":[{"given":"CURT J.","family":"REYNOLDS","sequence":"first","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"ALKIS","family":"TOGIAS","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DAVID","family":"PROUD","sequence":"additional","affiliation":[{"name":"Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1999,2,1]]},"reference":[{"key":"2026032708565534100_B1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev.iy.06.040188.000405","article-title":"Kinin formation: mechanisms and role in inflammatory disorders.","volume":"6","author":"Proud","year":"1988","journal-title":"Annu. Rev. Immunol."},{"key":"2026032708565534100_B2","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1172\/JCI111127","article-title":"Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.","volume":"72","author":"Proud","year":"1983","journal-title":"J. Clin. Invest."},{"key":"2026032708565534100_B3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1056\/NEJM198507113130201","article-title":"Inflammatory mediators in late antigen-induced rhinitis.","volume":"313","author":"Naclerio","year":"1985","journal-title":"N. Engl. J. Med."},{"key":"2026032708565534100_B4","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/0091-6749(90)90064-B","article-title":"Albumin, bradykinins, and eosinophil cationic protein on the nasal mucosal surface in patients with hay fever during natural allergen exposure.","volume":"85","author":"Svensson","year":"1990","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032708565534100_B5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1172\/JCI112782","article-title":"Detection of tissue kallikrein in the bronchoalveolar lavage fluid of asthmatic subjects.","volume":"79","author":"Christiansen","year":"1987","journal-title":"J. Clin. Invest."},{"key":"2026032708565534100_B6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1164\/ajrccm\/144.1.51","article-title":"Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics: cellular, mediator, and permeability changes.","volume":"144","author":"Liu","year":"1991","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708565534100_B7","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1164\/ajrccm\/137.3.613","article-title":"Nasal provocation with bradykinin induces symptoms of rhinitis and a sore throat.","volume":"137","author":"Proud","year":"1988","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708565534100_B8","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/0014-2999(90)90149-Z","article-title":"Vascular effects of topically applied bradykinin on the human nasal mucosa.","volume":"175","author":"Holmberg","year":"1990","journal-title":"Eur. J. Pharmacol."},{"key":"2026032708565534100_B9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1113\/jphysiol.1991.sp018612","article-title":"Comparative nasal effects of bradykinin, kallidin and [des-arg9]-bradykinin in atopic rhinitic and normal volunteers.","volume":"437","author":"Rajakulasingam","year":"1991","journal-title":"J. Physiol. (Lond.)"},{"key":"2026032708565534100_B10","first-page":"38","article-title":"The effects of bradykinin aerosol in guinea pigs and man.","volume":"158","author":"Herxheimer","year":"1961","journal-title":"J. Physiol. (Lond.)"},{"key":"2026032708565534100_B11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000230120","article-title":"The effect of inhalation of bradykinin on healthy and atopic (asthmatic) children.","volume":"34","author":"Varonier","year":"1968","journal-title":"Int. Arch. Allergy"},{"key":"2026032708565534100_B12","first-page":"176","article-title":"Bradykinin-induced bronchoconstriction in humans: mode of action.","volume":"135","author":"Fuller","year":"1987","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708565534100_B13","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/0162-3109(96)00065-3","article-title":"Efficacy and tolerability of icatibant (Hoe 140) in patients with moderately severe chronic bronchial asthma.","volume":"33","author":"Akbary","year":"1996","journal-title":"Immunopharmacology"},{"key":"2026032708565534100_B14","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1164\/ajrccm.153.1.8542147","article-title":"Airway responsiveness to bradykinin is related to eosinophilic inflammation in asthma.","volume":"153","author":"Roisman","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2026032708565534100_B15","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1152\/jappl.1995.78.5.1844","article-title":"Allergen-induced hyperresponsiveness to bradykinin is more pronounced than that to methacholine.","volume":"78","author":"Berman","year":"1995","journal-title":"J. Appl. Physiol."},{"key":"2026032708565534100_B16","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/S0091-6749(96)70193-8","article-title":"Evidence that enhanced nasal reactivity to bradykinin in patients with symptomatic allergy is mediated by neural reflexes.","volume":"97","author":"Riccio","year":"1996","journal-title":"J. Allergy Clin. Immunol."},{"key":"2026032708565534100_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0031-6997(25)06836-X","article-title":"Pharmacology of bradykinin and related kinins.","volume":"32","author":"Regoli","year":"1980","journal-title":"Pharmacol. Rev."},{"key":"2026032708565534100_B18","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/0006-291X(92)91187-U","article-title":"Cloning and pharmacological characterization of a human bradykinin (BK\u20132) receptor.","volume":"184","author":"Hess","year":"1992","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026032708565534100_B19","doi-asserted-by":"crossref","first-page":"21583","DOI":"10.1016\/S0021-9258(17)31844-6","article-title":"Expression cloning of a human B1 bradykinin receptor.","volume":"269","author":"Menke","year":"1994","journal-title":"J. Biol. Chem."},{"key":"2026032708565534100_B20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0162-3109(95)00011-H","article-title":"Kinin B1 receptors: a review.","volume":"30","author":"Marceau","year":"1995","journal-title":"Immunopharmacology"},{"key":"2026032708565534100_B21","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/0166-2236(93)90133-7","article-title":"Bradykinin and inflammatory pain.","volume":"16","author":"Dray","year":"1993","journal-title":"Trends Neurosci."},{"key":"2026032708565534100_B22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1476-5381.1994.tb16174.x","article-title":"The involvement of bradykinin B1 and B2 receptor mechanisms in cytokine-induced mechanical hyperalgesia in the rat.","volume":"113","author":"Davis","year":"1994","journal-title":"Br. J. Pharmacol."},{"key":"2026032708565534100_B23","doi-asserted-by":"crossref","first-page":"428","DOI":"10.4049\/jimmunol.138.2.428","article-title":"Kinin metabolism in human nasal secretions during experimentally induced allergic rhinitis.","volume":"138","author":"Proud","year":"1987","journal-title":"J. Immunol."},{"key":"2026032708565534100_B24","doi-asserted-by":"crossref","first-page":"11420","DOI":"10.1074\/jbc.272.17.11420","article-title":"Stable expression of the human kinin B1 receptor in Chinese Hamster Ovary cells: characterization of ligand binding and effector pathways.","volume":"272","author":"Austin","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2026032708565534100_B25","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1164\/ajrccm\/142.6_Pt_1.1367","article-title":"Comparative airway response to inhaled bradykinin, kallidin, and [des-Arg9]bradykinin in normal and asthmatic subjects.","volume":"142","author":"Polosa","year":"1990","journal-title":"Am. Rev. Respir. Dis."},{"key":"2026032708565534100_B26","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1159\/000235469","article-title":"Pharmacology of nasal provocation with bradykinin: studies of tachyphylaxis, cyclooxygenase inhibition, alpha-adrenergic stimulation, and receptor subtype.","volume":"95","author":"Churchill","year":"1991","journal-title":"Int. Arch. Allergy Appl. Immunol."},{"key":"2026032708565534100_B27"},{"key":"2026032708565534100_B28","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1074\/jbc.273.5.2617","article-title":"Influence of the cytosolic carboxy termini of human B1 and B2 kinin receptors on receptor sequestration, ligand internalization and signal transduction.","volume":"272","author":"Faussner","year":"1998","journal-title":"J. Biol. Chem."},{"key":"2026032708565534100_B29","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1172\/JCI119039","article-title":"Induction of tachykinin gene and peptide expression in guinea pig nodose primary afferent neurons by allergic airway inflammation.","volume":"98","author":"Fischer","year":"1996","journal-title":"J. Clin. Invest."},{"key":"2026032708565534100_B30","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1111\/j.1365-2222.1997.tb01178.x","article-title":"Substance P is generated in vivo following nasal challenge of allergic individuals with bradykinin.","volume":"27","author":"Baumgarten","year":"1997","journal-title":"Clin. Exp. Allergy"},{"key":"2026032708565534100_B31","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1136\/thx.50.3.225","article-title":"Effects of topical capsaicin in seasonal allergic rhinitis.","volume":"50","author":"Greiff","year":"1995","journal-title":"Thorax"},{"key":"2026032708565534100_B32","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1046\/j.1365-2222.1998.00182.x","article-title":"Comparison of nasal mucosal responsiveness to neuronal stimulation in non-allergic and allergic rhinitis: effects of capsaicin nasal challenge.","volume":"28","author":"Sanico","year":"1998","journal-title":"Clin. Exp. Allergy"},{"key":"2026032708565534100_B33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1152\/jappl.1998.84.2.537","article-title":"Plasma extravasation through neuronal stimulation in human nasal mucosa in the setting of allergic rhinitis.","volume":"84","author":"Sanico","year":"1998","journal-title":"J. Appl. Physiol."},{"key":"2026032708565534100_B34","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1113\/jphysiol.1996.sp021234","article-title":"Immunomodulation of afferent neurons in guinea-pig isolated airway.","volume":"491","author":"Riccio","year":"1996","journal-title":"J. Physiol."}],"container-title":["American Journal of Respiratory and Critical Care Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/159\/2\/431\/67430157\/ajrccm_159_2_431.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ajrccm\/article-pdf\/159\/2\/431\/67430157\/ajrccm_159_2_431.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T12:57:07Z","timestamp":1774616227000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajrccm\/article\/159\/2\/431\/8530118"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,2,1]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[1999,2,1]]},"published-print":{"date-parts":[[1999,2,1]]}},"URL":"https:\/\/doi.org\/10.1164\/ajrccm.159.2.9804132","relation":{},"ISSN":["1073-449X","1535-4970"],"issn-type":[{"value":"1073-449X","type":"print"},{"value":"1535-4970","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[1999,2]]},"published":{"date-parts":[[1999,2,1]]}}}