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Title: Characterisation of the kinin receptor in the human nasal airway and its role in allergic rhinitis
Author: Dear, James William
ISNI:       0000 0001 3421 2114
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1996
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This thesis presents an investigation into the characteristics of the bradykinin receptor in the human nasal airway. There is evidence that bradykinin is a mediator of allergic rhinitis; an allergen-induced inflammatory disorder of the nasal airway. Intranasal administration of bradykinin induces some of the symptoms of allergic rhinitis. The effect of a variety of bradykinin receptor antagonists on the actions of bradykinin in the human nasal airway in vivo is investigated. This characterisation of the human nasal bradykinin receptor is extended by performing radioligand binding experiments using ex vivo human nasal tissue. Using these two different experimental approaches, the nasal bradykinin receptor appears to be of the B2 type. Using atopic human subjects, the effect of the bradykinin receptor antagonist, icatibant, on experimentally-induced seasonal and perennial allergic rhinitis provides data strongly implicating bradykinin in the pathophysiology of perennial allergic rhinitis. The role of nitric oxide in the nasal response to bradykinin, histamine and antigen is also investigated by inhibiting nitric oxide generation in the human nasal cavity. Bradykinin has been shown in other systems to release histamine from mast cells. The effect of histamine H1 receptor antagonists on the nasal actions of bradykinin is investigated, as is the effect of bradykinin on histamine release from ex vivo human nasal tissue. From these experiments both nitric oxide and histamine appear to mediate, at least in part, the response of the human nasal cavity to bradykinin challenge. Nitric oxide also appears to be a mediator of experimentally-induced allergic rhinitis. Platelet activating factor (PAF) is a mediator of inflammation which appears to be generated in allergic rhinitis. If PAF is administered to a normal, non-atopic, human nasal cavity it increases the responsiveness of the airway to histamine and bradykinin. The final chapter of this thesis implicates a role for kinin generation in PAF-induced human nasal hyperresponsiveness.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Bradykinin receptor