- Peptide CTAENTLFYVKES, corresponding to amino acid residues 270-282 of human P2Y12 receptor (Accession Q9H244). 3rd extracellular loop.
- Mouse BV-2 microglia cells; human MEG-01 megakaryoblastic leukemia cells (2.5-5 µg).
- Cell surface detection of P2Y12 in live intact mouse BV-2 microglia cells:___ Cells.
___ Cells + rabbit IgG isotype control-PE.
___ Cells + Anti-P2Y12 Receptor (extracellular)-PE Antibody (#APR-020-PE), (2.5 µg).
The P2Y receptors are a widely expressed group of G-protein coupled receptors (GPCRs). P2Y receptors are activated by nucleotides which are extracellular signaling molecules that are released from damaged cells or secreted via non-lytic mechanisms during inflammation, ischemia or hypoxia.
P2Y12 receptor, like all P2Y receptors, is a 7-membrane spanning protein coupled to a G protein. Most of the seven transmembrane helices of P2YR12 are not perpendicular to the plane of the membrane but are tilted or kinked. The carboxy-terminal helix VIII is parallel to the membrane lipid bilayer. The receptor contains 342 amino acid residues and two potential N-linked glycosylation sites at its extra-cellular amino terminus, which may modulate its activity.
ADP and some of its analogues stimulate P2YR12-mediated inhibition of adenylyl cyclase through activation of the Gαi2 G protein subtype, although effective coupling may also occur to Gαi1 G and Gαi3 G.
P2YR12 is an important cofactor of platelet aggregation and secretion induced by several agonists including collagen, TXA2, thrombin and specific antibodies cross-linking FcγRIIa receptors. It also plays an important role in shear-induced platelet aggregation and in platelet thrombus formation and stabilization on collagen-coated surfaces or ruptured atherosclerotic plaques under flow conditions.
Inherited abnormalities of P2YR12 include an autosomal recessive disorder causing severe receptor deficiency. Due to this abnormality, ADP, even at very high concentrations, does not induce full and irreversible platelet aggregation, nor does it inhibit the stimulation of platelet adenylyl cyclase causing excessive bleeding and additional coagulative dysfunction.