Abstract
Platelet expressed G protein-coupled receptors (GPCRs) are critical regulators of platelet function. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis associated with coronary atherosclerosis and ischaemic stroke. However, anti-thrombotic drug therapy is associated with high inter-patient variability in therapeutic response and adverse bleeding side-effects. In order to optimise the use of existing antiplatelet drugs and to develop new therapies more detailed knowledge is required relating to the molecular mechanisms that regulate GPCR and therefore platelet function. One approach has been to identify rare, function-disrupting mutations within key platelet proteins in patients with bleeding disorders. In this review we describe how an integrated functional genomics strategy has contributed important structure-function information about platelet GPCRs with specific emphasis upon purinergic (P2Y12 ) and thromboxane (TP-α) receptors. We also discuss the potential implications these findings have for pharmacotherapy and for understanding the molecular basis of mild bleeding disorders.
Original language | English |
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Journal | British Journal of Pharmacology |
Early online date | 24 Nov 2014 |
DOIs | |
Publication status | Published - 2015 |
Keywords
- platelet function
- antiplatelet drugs
- G protein-coupled receptors