P2Y receptors mediate the actions of the extracellular nucleotides (ATP, ADP, UTP and UDP) and regulate several physiologic responses, among them, cardiac function, platelet aggregation and SMC proliferation.1 The metabotropic P2Y receptors belong to the G-protein-coupled receptor (GPCR) superfamily. The P2Y receptor group currently includes the cloned mammalian receptors P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and the UDP-glucose receptor, now renamed P2Y142-4.
The P2Y6 receptor
The P2Y6 receptor is a member of the G-protein-coupled P2Y purinergic receptor family that is preferentially activated by UDP. Relatively little is known regarding its function although recently several reports discussing potential roles for the P2Y6 receptor have been published. Activation of the P2Y6 receptor in 1321N1 astrocytes was reported to have an anti-apoptotic effect, possibly via activation of PKC which controls Erk phosphorylation5. The P2Y6 receptor was also reported to have a prominent role in mediating contractions of cerebral arteries. The marked effect of the P2Y6 receptor in the cerebral circulation might make it a suitable target for treatment of diseases associated with cerebral vasospasm6.
The P2Y12 receptor
The P2Y12 receptor is co-expressed with the P2Y1 receptor on platelets. Their activation leads to platelet shape change, aggregation, and a rise in intracellular Ca2+. The P2Y12 receptor is expressed only in brain and platelets, according to results from reverse transcription polymerase chain reaction and northern blotting experiments7. The P2Y12 receptor has become a target for potential therapeutic drugs for the treatment of thromboembolism and other clotting disorders7.
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