Purinergic nucleotides, such as adenosine and uracil mono-, di- and triphosphates (AMP, ADP, ATP, UMP, UDP, UTP) regulate a broad range of physiological processes, but they have a central role in the primary haemostasis. Following the endothelial injury, platelets adhere to the exposed subendothelial structures and release ADP and ATP, stored in large concentrations in their intracellular granules. These nucleotides, interacting by their cell-surface purinergic platelet membrane receptors (P2X2, P2Y1 and P2Y12 receptors) amplify the ongoing platelet activation, recruit more platelets to the site of the injury resulting in firm platelet adhesion, platelet shape change, irreversible aggregation and expression of the procoagulant activity. Finally, occlusive, stable thrombi are formed and the primary haemostasis is restored. ADP plays a crucial role by enhancing these processes via the P2Y12 receptor. Importantly, under pathological conditions like thrombus formation after the rupture of the atherosclerotic plaque, the elementary contribution of the P2Y12 receptor is maintained. This mechanism explains the antiplatelet effectiveness of the thienopyridine derivatives (ticlopidine and clopidogrel), acting via the irreversible blockade of the P2Y12 receptor. These drugs are currently one of the most important components in the treatment of the cardiovascular disease.
|Translated title of the contribution||P2 purinergic receptors: Physiology and pathophysiology in thrombogenesis|
|Number of pages||11|
|Publication status||Published - Dec 1 2004|
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