Antihyperalgesic activity of a novel nonpeptide bradykinin B 1 receptor antagonist in transgenic mice expressing the human B 1 receptor

Fox, A, Kaur, S, Li, B, Panesar, M, Saha, U, Davis, C, Dragoni, i, Colley, S, Richie, T, Bevan, S, Burgess, G and McIntyre, P 2005, 'Antihyperalgesic activity of a novel nonpeptide bradykinin B 1 receptor antagonist in transgenic mice expressing the human B 1 receptor', British Journal of Pharmacology, vol. 144, no. 7, pp. 889-899.


Document type: Journal Article
Collection: Journal Articles

Title Antihyperalgesic activity of a novel nonpeptide bradykinin B 1 receptor antagonist in transgenic mice expressing the human B 1 receptor
Author(s) Fox, A
Kaur, S
Li, B
Panesar, M
Saha, U
Davis, C
Dragoni, i
Colley, S
Richie, T
Bevan, S
Burgess, G
McIntyre, P
Year 2005
Journal name British Journal of Pharmacology
Volume number 144
Issue number 7
Start page 889
End page 899
Total pages 11
Publisher John Wiley and Sons
Abstract We describe the properties of a novel nonpeptide kinin B 1 receptor antagonist, NVP-SAA164, and demonstrate its in vivo activity in models of inflammatory pain in transgenic mice expressing the human B 1 receptor. NVP-SAA164 showed high affinity for the human B 1 receptor expressed in HEK293 cells (K i 8 nM), and inhibited increases in intracellular calcium induced by desArg 10kallidin (desArg 10KD) (IC 50 33 nM). While a similar high affinity was observed in monkey fibroblasts (K i 7.7nM), NVP-SAA164 showed no affinity for the rat B 1 receptor expressed in Cos-7 cells. In transgenic mice in which the native B 1 receptor was deleted and the gene encoding the human B 1 receptor was inserted (hB 1 knockin, hB 1-KI), hB 1 receptor mRNA was induced in tissues following LPS treatment. No mRNA encoding the mouse or human B 1 receptor was detected in mouse B 1 receptor knockout (mB 1-KO) mice following LPS treatment. Freund's complete adjuvant-induced mechanical hyperalgesia was similar in wild-type and hB 1-KI mice, but was significantly reduced in mB 1-KO animals. Mechanical hyperalgesia induced by injection of the B 1 agonist desArg 10KD into the contralateral paw 24h following FCA injection was similar in wild-type and hB 1-KI mice, but was absent in mB 1-KO animals
Subject Pharmacology and Pharmaceutical Sciences not elsewhere classified
Keyword(s) Human B 1 receptor knockin
Hyperalgesia
Inflammation
Kinin B 1 receptor
DOI - identifier 10.1038/sj.bjp.0706139
Copyright notice © 2005 Nature Publishing Group. All rights reserved
ISSN 0007-1188
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