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Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma.
Allergy 1990; 45(3):174-82A

Abstract

Bradykinin, a nonapeptide cleavage product of high molecular weight kininogen, is a potent bronchoconstrictor agonist in asthma; however, its mechanism of action is not known. Since bradykinin has been shown to stimulate mediator release from mast cells and augment the release of prostanoids, we have examined the effect of a selective histamine H1 receptor antagonist, terfenadine and a potent cyclooxygenase inhibitor, flurbiprofen on bronchoconstriction provoked by inhaled bradykinin in asthma. As a bronchial provocation procedure bradykinin challenge was repeatable to within 1 doubling dilution. In nine atopic asthmatic subjects, terfenadine 180 mg, when compared to placebo, increased the geometric mean provocation concentration of inhaled agonist required to reduce FEV1 by 20% of baseline (PC20) from 0.7 to greater than 22.9 mg/ml for histamine (P less than 0.01) and 0.3 to 0.5 mg/ml for bradykinin (P less than 0.01). In a further nine atopic asthmatics, flurbiprofen 150 mg when compared to placebo produced a small but significant protection of the airways against bradykinin, geometric mean PC20 increasing from 0.40 to 0.79 mg/ml (P less than 0.05). We conclude that bradykinin is a potent bronchoconstrictor agonist in asthma, being approximately 9.5 times more potent than histamine in molar terms. Pharmacological intervention with terfenadine and flurbiprofen led to a significant protection of the airways against the constrictor effect of bradykinin but the effect in each case was small. Thus, while histamine and prostanoids may contribute as mediators of bradykinin-induced bronchoconstriction, they are unlikely to account for the majority of the response.

Authors+Show Affiliations

Immunopharmacology Group, Medicine 1 Level D, Southampton General Hospital, England.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Controlled Clinical Trial
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

1970226

Citation

Polosa, R, et al. "Contribution of Histamine and Prostanoids to Bronchoconstriction Provoked By Inhaled Bradykinin in Atopic Asthma." Allergy, vol. 45, no. 3, 1990, pp. 174-82.
Polosa R, Phillips GD, Lai CK, et al. Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma. Allergy. 1990;45(3):174-82.
Polosa, R., Phillips, G. D., Lai, C. K., & Holgate, S. T. (1990). Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma. Allergy, 45(3), pp. 174-82.
Polosa R, et al. Contribution of Histamine and Prostanoids to Bronchoconstriction Provoked By Inhaled Bradykinin in Atopic Asthma. Allergy. 1990;45(3):174-82. PubMed PMID: 1970226.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Contribution of histamine and prostanoids to bronchoconstriction provoked by inhaled bradykinin in atopic asthma. AU - Polosa,R, AU - Phillips,G D, AU - Lai,C K, AU - Holgate,S T, PY - 1990/4/1/pubmed PY - 1990/4/1/medline PY - 1990/4/1/entrez SP - 174 EP - 82 JF - Allergy JO - Allergy VL - 45 IS - 3 N2 - Bradykinin, a nonapeptide cleavage product of high molecular weight kininogen, is a potent bronchoconstrictor agonist in asthma; however, its mechanism of action is not known. Since bradykinin has been shown to stimulate mediator release from mast cells and augment the release of prostanoids, we have examined the effect of a selective histamine H1 receptor antagonist, terfenadine and a potent cyclooxygenase inhibitor, flurbiprofen on bronchoconstriction provoked by inhaled bradykinin in asthma. As a bronchial provocation procedure bradykinin challenge was repeatable to within 1 doubling dilution. In nine atopic asthmatic subjects, terfenadine 180 mg, when compared to placebo, increased the geometric mean provocation concentration of inhaled agonist required to reduce FEV1 by 20% of baseline (PC20) from 0.7 to greater than 22.9 mg/ml for histamine (P less than 0.01) and 0.3 to 0.5 mg/ml for bradykinin (P less than 0.01). In a further nine atopic asthmatics, flurbiprofen 150 mg when compared to placebo produced a small but significant protection of the airways against bradykinin, geometric mean PC20 increasing from 0.40 to 0.79 mg/ml (P less than 0.05). We conclude that bradykinin is a potent bronchoconstrictor agonist in asthma, being approximately 9.5 times more potent than histamine in molar terms. Pharmacological intervention with terfenadine and flurbiprofen led to a significant protection of the airways against the constrictor effect of bradykinin but the effect in each case was small. Thus, while histamine and prostanoids may contribute as mediators of bradykinin-induced bronchoconstriction, they are unlikely to account for the majority of the response. SN - 0105-4538 UR - https://www.unboundmedicine.com/medline/citation/1970226/Contribution_of_histamine_and_prostanoids_to_bronchoconstriction_provoked_by_inhaled_bradykinin_in_atopic_asthma_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0105-4538&date=1990&volume=45&issue=3&spage=174 DB - PRIME DP - Unbound Medicine ER -