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An investigation into the roles of histamine receptors in the control of human nasal blockage

Taylor-Clark, TE; (2004) An investigation into the roles of histamine receptors in the control of human nasal blockage. Doctoral thesis, University of London. Green open access

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Abstract

Allergic rhinitis is an allergic disease of the nose and, in sensitized individuals, is caused by inhaled innocuous particles such as pollen and house dust mite faeces. Allergen binds IgE on the surface of nasal mast cells, causing mast cell activation and degranulation, resulting in the release of inflammatory substances that are responsible for the symptoms of allergic rhinitis — sneezing, rhinorrhea, pruritus and nasal blockage. In this thesis, the mechanisms by which histamine, a mast cell-derived inflammatory mediator released during allergen challenge, causes nasal blockage were investigated. In addition, the role of nasal sympathetic neurones in the control of nasal blockage was also investigated. The nasal blockage caused by inflammatory substances was assessed objectively by a technique called acoustic rhinometry. Subjects, either normal, healthy, individuals or atopic, allergic, individuals, were challenged with nasal aerosols of pollen, histamine or histamine receptor agonists, and their nasal responses were recorded. In this way, nasal blockage was shown to be caused by pollen, histamine, dimaprit (H2 receptor agonist) and R-a-methylhistamine (H3 receptor agonist). In addition, various histamine receptor antagonists were administered to the subjects to investigate to what extent these drugs affected responses to nasal challenge. Using this technique, histamine-induced nasal blockage was shown to be sensitive to Hl, H2 and H3 antagonists and pollen-induced nasal blockage was shown to be insensitive to H, and H2 antagonists. Both noradrenaline and 3,4-dihydroxyphenylglycol (noradrenaline metabolite) were measured in nasal lavages. Pharmacological interference of the sympathetic nervous system led to functional changes in human nasal patency. In particular, antagonism of aradrenoceptors caused nasal blockage. The presented data suggest that histamine causes nasal blockage via H1, H2 and H3 receptors. In addition, nasal sympathetic neurones were shown actively to maintain nasal patency and this was inhibited by activation of presynaptic H3 receptors.

Type: Thesis (Doctoral)
Title: An investigation into the roles of histamine receptors in the control of human nasal blockage
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
UCL classification: UCL > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
UCL > School of Life and Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1514475
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