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• W2063995128 abstract "1 The aim of this study was to characterize the kinin receptor in the human nasal airway using [125I]-Hoe 140 binding to a membrane preparation from human nasal turbinates and to compare Ki values from binding displacement by antagonists with the functional effects of these drugs in vivo We also investigated the effect of Hoe 140 ([D-Arg°, HyP3, Thi5, D-Tic7, Oic8]-bradykinin), on bradykinin release into the nasal airway. 2 In a membrane preparation from human nasal turbinates removed during surgery, [125I]-Hoe 140 labelled a single, saturable binding site. The equilibrium dissociation constant (at 20°C) for [125I]-Hoe 140 binding to the receptor was 0.46 ± 0.08 nM. The Bmax was 0.136 ± 0.003 pmol mg−1 protein and the Hill coefficient was 1.01 ± 0.07. 3 The association rate constant for [125I]-Hoe 140 binding to the receptor was 0.20 ± 0.06 nM−1 min−1 and the dissociation rate constant was 0.14 ± 0.01 min−1. These values were determined at 4°C. The equilibrium dissociation constant calculated from these rate constants was 0.70 nM. 4 Bradykinin and the B2 receptor antagonists, NPC 567, NPC 17731, NPC 17761, [1-adamantane acetyl-D-Arg°, Hyp3, Thi5, 8, D-Phe7]-bradykinin, WIN 64338 and Hoe 140 displaced [125I]-Hoe 140 binding: the Ki values from binding displacement are consistent with values expected from a B2 receptor. The B1 agonist, [des-Arg9]-bradykinin and the B1 antagonist, [des-Arg9]-Hoe 140 failed to displace [125I]-Hoe 140 binding at concentrations up to 1 μm. 5 The bradykinin antagonist, Hoe 140, 10 to 200 μg, given by intranasal aerosol, produced a dose-related inhibition of the reduction in minimal nasal cross-sectional area (Amin) induced by bradykinin in normal subjects and by house dust mite antigen in subjects with allergic rhinitis to house dust mite. Hoe 140, 10 to 200 μg, also caused a dose-related inhibition of the release of albumin into the nasal cavity following challenge with bradykinin. 6 [1-Adamantane acetyl-D-Arg°, Hyp3, Thi5, 8, D-Phe7]-bradykinin, 30 to 200 μg, caused a dose-related inhibition of the reduction in Amin and the release of albumin into the nasal cavity induced by bradykinin. NPC 567 ([D-Arg°, Hyp3, D-Phe7]-bradykinin) failed to inhibit the reduction in Amin or the release of albumin into the nasal cavity at a dose of 10 mg. 7 Challenge of allergic subjects with house dust mite antigen caused a significant elevation of the bradykinin concentration in nasal lavage fluid and a reduction in Amin. Hoe 140, 100 μg, prevented the antigen-induced reduction in Amin and also abolished the antigen-induced increase of bradykinin in nasal lavage fluid. 8 We conclude that there is a B2 bradykinin receptor in the human nasal airway which mediates nasal blockage and plasma extravasation induced by either bradykinin or antigen challenge. It is possible that Hoe 140 inhibits kallikrein in the human nasal airway as well as blocking the B2 receptor." @default.
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• W2063995128 date "1996-11-01" @default.
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• W2063995128 title "Characterization of the bradykinin receptor in the human nasal airway using the binding of [125I]-Hoe 140" @default.
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• W2063995128 doi "https://doi.org/10.1111/j.1476-5381.1996.tb15777.x" @default.
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