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Am. J. Respir. Crit. Care Med., Volume 160, Number 5, November 1999, 1717-1723

Contribution of Bradykinin B1 and B2 Receptors in Allergen-induced Bronchial Hyperresponsiveness

TUNG-JUNG HUANG, EL-BDAOUI HADDAD, ALYSON J. FOX, MICHAEL SALMON, CAROLINE JONES, GILLIAN BURGESS, and KIAN FAN CHUNG

Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom; Thoracic Medicine, Chang Gung Memorial Hospital, Keelung Branch, Taiwan, Republic of China; and Novartis Institute for Medical Research, London, United Kingdom

Bradykinin (BK) is a peptide mediator generated at sites of inflammation and its effects are mediated through constitutively expressed B2 receptor or through induction of B1 receptors. We examined the role of these receptors in bronchial hyperresponsiveness (BHR). Brown-Norway rats sensitized with ovalbumin (OA) and Al(OH)3 intraperitoneally, were exposed 3 wk later to either saline or OA aerosol. B1 receptor antagonist desArg10[Hoe140] (200 nmol/kg or 1 µmol/kg, intraperitoneally) or B2 receptor antagonist Hoe140 (200 nmol/kg, intraperitoneally) was administered 30 min before allergen exposure. Hoe140 had no effect on OA-induced BHR to acetylcholine (ACh) and bronchoalveolar lavage fluid (BALF) cellular profiles, but inhibited bronchoconstriction to BK (p < 0.04). At both doses, desArg10[Hoe140] dose-dependently inhibited allergen-induced BHR to ACh (p < 0.01), but had no effect on bronchoconstriction to BK or baseline ACh responsiveness. The inflammatory cells in BALF were not affected apart from reduced lymphocyte numbers at the highest dose. B1 receptor mRNA expression measured by Northern analysis was increased after allergen exposure in sensitized lungs, with a peak at 2 to 6 h after exposure, whereas B2 receptor mRNA expression remained unchanged. Newly induced BK B1 receptors may be involved in allergen-induced BHR to ACh, whereas constitutive B2 receptors mediate BK-induced bronchoconstriction. Huang T-J, Haddad E-B, Fox AJ, Salmon M, Jones C, Burgess G, Chung KF. Contribution of bradykinin B1 and B2 receptors in allergen-induced bronchial hyperresponsiveness.




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