Disease relevance of P2RY6

• Attenuation of signal flow from P2Y6 receptor by protein kinase C-alpha in SK-N-BE(2)C human neuroblastoma cells [1].
• Interestingly, UDP induces the production of IL-8, but not TNF-alpha, in human astrocytoma 1321N1 cell lines stably transfected with hP2Y6 [2].
• Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease [3].
• The P2Y6 receptor might be a suitable target for the treatment of cerebral vasospasm [4].
• The P2Y6 receptor appears to be identical to the uridine nucleotide-specific receptor previously characterized in C6-2B rat glioma cells [5].

High impact information on P2RY6

• Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production [6].
• These events were mediated primarily by P2Y receptors, specifically the P2Y2 and/or P2Y6 subclass of receptors [7].
• Agonist-promoted regulation of the uridine nucleotide-activated human P2Y4 receptor (P2Y4-R) and P2Y6 receptor (P2Y6-R) was studied [8].
• This receptor, designated P2Y7, has 352 amino acids and shares 23-30% amino acid identity with the P2Y1-P2Y6 purinoceptors [9].
• The P2Y6-receptor has a widespread distribution including heart, blood vessels, and brain [10].

Chemical compound and disease context of P2RY6

• 2. Cell death was induced in 1321N1 astrocytoma cells permanently expressing the rat P2Y6 receptor by exposure to TNFalpha in the presence of cycloheximide [11].

Biological context of P2RY6

• By fluorescence in situ hybridization and utilization of the National Center for Biotechnology Information (NCBI) database, the human P2Y6 gene was localized to chromosome 11q13.5, between polymorphic markers D11S1314 and D11S916 [12].
• Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues [13].
• 5. Oligonucleotide primers complementary to a part of the human P2Y6 receptor cDNA were used to amplify a region from genomic DNA from a panel of mouse/human somatic cell hybrid cell lines, each containing a single human chromosome [14].
• IC50 values at P2Y1 and P2Y6 receptors were <1 microM [15].
• Differential regulation of the uridine nucleotide-activated P2Y4 and P2Y6 receptors. SER-333 and SER-334 in the carboxyl terminus are involved in agonist-dependent phosphorylation desensitization and internalization of the P2Y4 receptor [8].

Anatomical context of P2RY6

• Applications with ATP and UTP revealed that luminal membranes of NHNE cells express P2Y2 and P2Y6 receptors and basolateral membranes express P2Y2 receptor [16].
• Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway [6].
• The distribution of the P2Y6-receptor is widespread including heart, blood vessels and brain [17].
• Recently, the hP2Y6 receptor has been reported to mediate monocyte IL-8 production in response to UDP or lipopolysaccharide (LPS), but the role of hP2Y6 in regulating other pro-inflammatory cytokines or mediators is largely unknown [2].
• Here, we studied the biological activity of the selective purinoreceptor P2Y6 (P2YR6) agonist Uridine 5'diphosphate (UDP) as well as the P2YR2- and P2YR4-activating uridine 5'triphosphate (UTP) on human dendritic cells (DC) [18].

Associations of P2RY6 with chemical compounds

• Neuronal differentiation of the cells by treatment with retinoic acid for 7 days did not change the expression level of P2Y6 receptors [1].
• The nucleotide efficacy profile [ATP = ADP > UDP >or= UTP > adenosine >or= 2-methylthioadenosine-5'-diphosphate, with alpha,beta-methylene adenosine 5'-triphosphate, 2',3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate, AMP, UMP, and ATPalphaS inactive] and PCR analysis indicate involvement of P2Y2 and P2Y6 receptors [19].
• 3. Inositol trisphosphates assays have identified a response typical of the P2Y2 receptor in the 1HAEo- and the 16HBE14o- airway epithelial cell lines which co-express P2Y2 and P2Y6 mRNA [20].
• These results define the uridine nucleotide selectivity of three phospholipase C-linked receptors: a receptor that is selectively activated by UDP (P2Y6 receptor), selectively activated by UTP (P2Y4 receptor), and activated by UTP and ATP but not by diphosphate nucleotides (P2Y2 receptor) [21].
• Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors [22].

Other interactions of P2RY6

• Expressions of P2Y2 and P2Y6 receptors in NHNE cells were further verified by immunoblotting using specific antibodies [16].
• With the recent discovery of several new members from a variety of species, the P2Y purinoceptor family now encompasses types P2Y1 to P2Y6 [12].
• The human P2Y6 receptor (hP2Y6) is a member of the G protein-coupled pyrimidinergic P2 receptor family that responds specifically to the extracellular nucleotide uridine diphosphate (UDP) [2].
• UDP activation of P2Y6 provoked: (a) an increase in free cytosolic calcium; (b) the activation of protein kinase C-alpha, -beta, -delta, -epsilon, and -zeta but not of PKC-iota and -eta; (c) the phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2); (d) the expression of c-Fos protein [23].
• In smooth muscle cells (SMCs), high shear stress decreased P2X1 receptors, whereas P2Y2 and P2Y6 receptors were upregulated [24].

Analytical, diagnostic and therapeutic context of P2RY6

• Using a degenerate PCR approach on MG-63 cell cDNA we found PCR fragments coding for human P2Y1 and a new receptor, P2Y6. cDNA cloning of the P2Y6 receptor identified three cDNA isoforms [25].
• In this study, we have examined the expression of P2Y6 in a range of tissues containing leukocytes by a combination of in situ hybridization (ISH), Northern blot analysis, and RT-PCR [3].
• The expression of mRNA for P2Y2 and P2Y6 receptors was demonstrated by RT-PCR [26].
• Presence of P2Y6 receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man [27].

References