Journal ArticleDOI
International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences
L. M. Fredrik Leeb-Lundberg,François Marceau,Werner Müller-Esterl,Douglas J. Pettibone,Bruce L. Zuraw +4 more
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TLDR
This review is a comprehensive presentation of the current understanding of B1 and B2 receptors in terms of molecular and cell biology, physiology, pharmacology, and involvement in human disease and drug development.Abstract:
Kinins are proinflammatory peptides that mediate numerous vascular and pain responses to tissue injury. Two pharmacologically distinct kinin receptor subtypes have been identified and characterized for these peptides, which are named B1 and B2 and belong to the rhodopsin family of G protein-coupled receptors. The B2 receptor mediates the action of bradykinin (BK) and lysyl-bradykinin (Lys-BK), the first set of bioactive kinins formed in response to injury from kininogen precursors through the actions of plasma and tissue kallikreins, whereas the B(1) receptor mediates the action of des-Arg9-BK and Lys-des-Arg9-BK, the second set of bioactive kinins formed through the actions of carboxypeptidases on BK and Lys-BK, respectively. The B2 receptor is ubiquitous and constitutively expressed, whereas the B1 receptor is expressed at a very low level in healthy tissues but induced following injury by various proinflammatory cytokines such as interleukin-1beta. Both receptors act through G alpha(q) to stimulate phospholipase C beta followed by phosphoinositide hydrolysis and intracellular free Ca2+ mobilization and through G alpha(i) to inhibit adenylate cyclase and stimulate the mitogen-activated protein kinase pathways. The use of mice lacking each receptor gene and various specific peptidic and nonpeptidic antagonists have implicated both B1 and B2 receptors as potential therapeutic targets in several pathophysiological events related to inflammation such as pain, sepsis, allergic asthma, rhinitis, and edema, as well as diabetes and cancer. This review is a comprehensive presentation of our current understanding of these receptors in terms of molecular and cell biology, physiology, pharmacology, and involvement in human disease and drug development.read more
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Mammalian G proteins and their cell type specific functions
TL;DR: In this review, some of the functions of heterotrimeric G proteins in defined cells and tissues are described.
Journal ArticleDOI
Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo
Felicitas Müller,Nicola J. Mutch,Wolfdieter A. Schenk,Stephanie A. Smith,Lucie Esterl,Henri M. H. Spronk,Stefan Schmidbauer,William A. Gahl,James H. Morrissey,Thomas Renné +9 more
TL;DR: The data identify polyP as a new class of mediator having fundamental roles in platelet-driven proinflammatory and procoagulant disorders, including Hermansky-Pudlak Syndrome patients, who lack platelet polyP.
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The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors
Stephen P.H. Alexander,Helen E. Benson,Elena Faccenda,Adam J. Pawson,Joanna L. Sharman,Michael Spedding,John A. Peters,Anthony J. Harmar +7 more
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The kallikrein-kinin system: current and future pharmacological targets.
Marie Eve Moreau,Nancy Garbacki,Giuseppe Molinaro,Nancy J. Brown,François Marceau,Albert Adam +5 more
TL;DR: The main properties of this kallikrein-kinin system are summarized and the multiple pharmacological interventions that modulate the functions of this system, restraining its proinflammatory effects or potentiating its cardiovascular properties are addressed.
Journal ArticleDOI
G protein-coupled receptors sense fluid shear stress in endothelial cells
TL;DR: It is shown that mechanical perturbation of the plasma membrane leads to ligand-independent conformational transitions in a G protein-coupled receptor (GPCR), and it is suggested that GPCRs are involved in mediating primary mechanochemical signal transduction in endothelial cells.
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