Reduction by Hoe 140, the B₂ kinin receptor antagonist, of antigen‐induced nasal blockage

Abstract

In subjects with allergic rhinitis to house-dust mite (HDM), antigen challenge produced a significant increase in nasal blockage but had no effect on nasal vascular permeability. The B2 kinin receptor antagonist, [D-Arg0,Hyp3,Thi5,D-Tic7,Oic8]-bradykinin (Hoe 140), 200 Lg administered by intranasal aerosol 2 min prior to challenge with HDM, 500 u significantly reduced nasal blockage induced by the antigen challenge. The data are compatible with a role for B2 kinin receptors in the nasal response to challenge with antigen which is responsible for nasal blockage.

Characterization of the bradykinin receptor in the human nasal airway using the binding of [125I]‐Hoe 140

“…Unlabelled Hoe 140 and NPC 567 also fully displaced the specific binding of ['251 Table 2 shows the bradykinin concentrations recovered by nasal lavage and the changes in Amin following house dust mite antigen challenge of subjects with allergic rhinitis. As previously reported, house dust mite antigen challenge significantly reduced the Amin (Austin et al, 1994 binding curve at 20°C (0.48 nM) and, independently from the association and dissociation rate constants at 40C (0.70 nM), are consistent with estimates in human lung of 0.73 nM (Trifilieff et al, 1994) and in guinea-pig ileum of 0.79 nm (Hock et al, 1991). The presence of multiple ['251]-Hoe 140 binding sites on the human nasal membranes cannot be excluded by using only a low concentration of radioligand in displacement studies as there may be high and low affinity binding sites for [1251]-Hoe 140, as proposed for guinea-pig lung and brain (Sequin et al, 1992).…”

“…Second, in normal, non-allergic subjects, challenge of the nasal airway with bradykinin, but not with B1 selective agonists, produces some of the signs of allergic rhinitis: namely, increased nasal airway resistance and increased vascular permeability of the nasal vasculature (Proud et al, 1988;Rajakulasingham et al, 1991;Austin & Foreman, 1994a). Third, in perennial allergic rhinitis caused by house dust mite antigen, the bradykinin receptor antagonist, Hoe 140 ([D-Arg', Hyp3, Thi5, D-Tic7, Oic8]-bradykinin; generic name, icatibant) blocks antigen-induced nasal blockage (Austin et al, 1994).…”

Tissue remodelling in upper airways: where is the link with lower airway remodelling?

“…Interestingly, the bulk exudation of plasma into the airway tissue (vascular exudation) and lumen (mucosal exudation) occurring during allergic rhinitis is limited and reversible. The albumin extravasation and consequent remodelling may be different in acute allergen exposure compared with chronic exposure (34). Increased angiogenesis has also been suspected (35,36).…”

Attenuation of human nasal airway responses to bradykinin and histamine by inhibitors of nitric oxide synthase

“…Application of bradykinin to the nasal airway of normal subjects causes increased nasal airway resistance and a decrease in the nasal cross-sectional area, together with the release of albumin into nasal washings (Proud et al, 1988;Rajakulasingham et al, 1991;Austin & Foreman, 1994a). Pretreatment with the bradykinin B2 receptor antagonist, icatibant (Hoe 140), of subjects with allergic rhinitis to house dust mite, reduces the nasal blockage which follows challenge with house dust mite antigen (Austin et al, 1994). Bradykinin does not mimic all of the features of allergic rhinitis but appears to be responsible mainly for increased nasal airway resistance and an increase in nasal vascular permeability.…”