(hCysLT2R) based on a β-galactosidase complementation
system. The EC50 values for LTC4 and LTD4 are consistent with previous literature
values determined based on radio-labelling affinity assays for hCysLT2R. Activity of a
synthetic analogue of LTC4, N-Methyl LTC4 (NMLTC4), gave an EC50 value of 8.5 nM.
Also described in this thesis, is the synthesis of a cysLT2R selective antagonist, 3-{[(3-
carboxycyclohexyl)amino]carbonyl}-4-{3-{4-(4-phenoxybutoxy)phenyl}-
propoxy}benzoic acid. Through the in vitro assay system, this selective antagonist
showed a dose-dependent inhibition (IC50 value of 86 nM) when CysLT2R was
stimulated with 30 nM of LTD4. Both the selective agonist (NMLTC4) as well as the
selective cysLT2R antagonist were also tested in vivo in a localized vascular ear
inflammation assay. Results show NMLTC4 is able to promote vascular leakage through
stimulation of cysLT2R, and this extravasation can be significantly attenuated by the cysLT2R antagonist. / Thesis (Master, Biochemistry) -- Queen's University, 2011-06-29 22:31:03.11
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OKQ.1974/6597 |
| Date | 06 July 2011 |
| Creators | YAN, DONG |
| Contributors | Queen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.)) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Rights | This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner. |
| Relation | Canadian theses |
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