کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2515302 | 1118511 | 2008 | 10 صفحه PDF | دانلود رایگان |
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.
Journal: Biochemical Pharmacology - Volume 75, Issue 9, 1 May 2008, Pages 1807–1816