Bradykinin receptors : agonists, antagonists, expression, signaling and adaptation to sustained stimulation

Authors: Marceau, FrançoisBouthillier, JohanneHoule, SteeveSabourin, ThierryFortin, Jean-PhilippeMorissette, GuillaumeLodge, RobertFortin, SébastienC. Gaudreault, RenéBawolak, Marie-ThérèseKoumbadinga, Gérémy AbdullRoy, CarolineCharest-Morin, Xavier; Gera, Lajos
Abstract: Bradykinin-related peptides, the kinins, are blood-derived peptides that stimulate 2 G protein–coupled receptors, the B1 and B2 receptors (B1R, B2R). The pharmacologic and molecular identities of these 2 receptor subtypes will be succinctly reviewed, with emphasis on drug development, receptor expression, signaling, and adaptation to persistent stimulation. Peptide and nonpeptide antagonists and fluorescent ligands have been produced for each receptor. The B2R is widely and constitutively expressed in mammalian tissues, whereas the B1R is mostly inducible under the effect of cytokines during infection and immunopathology. Both receptor subtypes mediate the vascular aspects of inflammation (vasodilation, edema formation). On this basis, icatibant, a peptide antagonist of the B2R, is approved in the management of hereditary angioedema attacks. Other clinical applications are still elusive despite the maturity of the medicinal chemistry efforts applied to kinin receptors. While both receptor subtypes are mainly coupled to the Gq protein and related second messengers, the B2R is temporarily desensitized by a cycle of phosphorylation/endocytosis followed by recycling, whereas the nonphosphorylable B1R is relatively resistant to desensitization and translocated to caveolae on activation.
Document Type: Article de recherche
Issue Date: 1 December 2013
Open Access Date: 20 November 2017
Document version: VoR
This document was published in: Journal of Angioedema, Vol. 1 (2), 9-17 (20130
Collection:Articles publiés dans des revues avec comité de lecture

Files in this item:
Description SizeFormat 
[R22]2013_JAngioedema.pdf571.9 kBAdobe PDFThumbnail
[R22]2013_JAngioedema_suppl_material.pdfMatériel supplémentaire250.55 kBAdobe PDFThumbnail
All documents in CorpusUL are protected by Copyright Act of Canada.