The inhibition of Bradykinin-induced Dermal inflammation by Cetirizine

Voegeli, D. (2001) The inhibition of Bradykinin-induced Dermal inflammation by Cetirizine. University of Southampton, School of Medicine, Doctoral Thesis.

Record type: Thesis (Doctoral)

Abstract

This work was designed to explore the effect of cetirizine on mediator release secondary to intradermal bradykinin challenge in normal human skin.
On intradermal injection, bradykinin produces a dose-dependant weal and flare response similar visually to that produced by histamine, suggesting that histamine release is involved in mediating the cutaneous response. This is further supported by the fact that premedication with cetirizine significantly inhibits both the bradykinin and histamine weal and flare. However microdialysis demonstrated that there is insignificant histamine release following bradykinin, and SLDI showed that the weal and flares produced by both histamine and bradykinin are different in nature, suggesting that other mediators, such as prostanoids or NO are involved. Although both prostanoid synthesis and NO release were observed following bradykinin, cetirizine failed to have any effect on the levels measured, suggesting that these are not the major mediators responsible for the bradykinin response.
Cetirizine was shown to be able to inhibit the cutaneous responses induced by a number of agonists, namely bradykinin, histamine, and methacholine. All of these act via a specific GPCR, and each one having an alpha subunit of the Gq/11 variety.
Therefore it is postulated that the bradykinin-induced weal and flare is mediated by activation of B2-kinin receptors located on sensory neurones, resulting in the release of neuropeptides, and that inhibition of this response is achieved by a direct inhibition of Gq/11 G-proteins, their regulatory proteins or modulation of a common second messenger system.

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