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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