title: Aspirin inhibits human bradykinin B2 receptor ligand binding function.
abstract: The bradykinin B2 receptor, a member of the G protein-coupled receptors superfamily, is involved in a variety of physiological functions, including vasodilation, electrolyte transfer in epithelia, mediation of pain, and inflammation. The effect of aspirin on bradykinin binding to cell-surface receptor and on signal transduction were studied in CHO-K1 cells, stably expressing the human B2 receptor. Cell-surface organization of the receptor was assessed by immunoprecipitation and Western blot analysis in CHO-K1 cells expressing N-terminally V5-tagged B2 receptor. We found that the widely used analgesic, anti-thrombotic, and anti-inflammatory drug aspirin alters the B2 receptor ligand binding properties. Aspirin reduces the apparent affinity of the receptor for [3H]-bradykinin by accelerating the dissociation rate of [3H]-bradykinin-receptor complexes. In addition, aspirin reduces the capacity of unlabeled bradykinin or the B2 receptor antagonist icatibant to destabilize pre-formed [3H]-bradykinin-receptor complexes. Kinetic and reversibility studies are consistent with an allosteric type of mechanism. Aspirin effect on B2 receptor binding properties is not accompanied by alteration of the cell-surface organization of the receptor in dimers and monomers. Aspirin does not influence the receptor ability to transduce bradykinin binding into activation of G-proteins and phospholipase C. These results suggest that aspirin is an allosteric inhibitor of the B2 receptor, a property that may be involved in its therapeutic actions.
authors: INSERM U652/U872, Paris-Descartes University, Paris, France.
authors: Joëlle
authors: J
authors: Gardes
authors: Stéphanie
authors: S
authors: Michineau
authors: Anne
authors: A
authors: Pizard
authors: François
authors: F
authors: Alhenc-Gelas
authors: Rabary M
authors: RM
authors: Rajerison
mesh_terms: D000495:Allosteric Site; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism; D065094:Bradykinin B2 Receptor Antagonists; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D007700:Kinetics; D008024:Ligands; D011485:Protein Binding; D011869:Radioligand Assay; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D065094:Bradykinin B2 Receptor Antagonists; D008024:Ligands; D010738:Type C Phospholipases; D001241:Aspirin; D001920:Bradykinin