Disease relevance of P2RY2

• Furthermore, UTP induced VCAM-1 expression in human 1321N1 astrocytoma cell transfectants expressing the recombinant P2Y2 receptor, whereas vector-transfected control cells did not respond to UTP [1].
• P2Y2 receptor up-regulation and activation induces intimal hyperplasia and monocyte/macrophage infiltration in the collared rabbit carotid artery model of vascular injury, suggesting a potential role for P2Y2 receptors in monocyte recruitment by vascular endothelium [1].
• P2X5 and P2Y2 receptors were heavily expressed in basal cell carcinomas and squamous cell carcinomas [2].
• Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacotherapy [3].
• In order to isolate new subtypes of P2 purinoceptors, sets of degenerate oligonucleotide primers were synthesized on the basis of the best conserved segments in the published sequences of the chick brain P2Y/P2Y1 and murine neuroblastoma P2U/P2Y2 receptors [4].

High impact information on P2RY2

• Up(4)A is likely to exert vasoconstriction predominantly through P2X1 receptors, and probably also through P2Y2 and P2Y4 receptors [5].
• Both pharmacological data and the occurrence of selectivity of coupling to second-messenger pathways indicate the existence of multiple members in several of the classes of P2-purinergic receptor subtypes [6].
• ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells [7].
• Mucin secretion was stimulated by extracellular adenosine 5'-triphosphate via P2U receptors, cytosolic calcium increase, and PKC and by taurochenodeoxycholate via cytosolic calcium increase and Ca2+/CaM-kinase II [8].
• RESULTS: Purinergic receptor agonists ATP and uridine triphosphate stimulated 125I and 86Rb efflux about twofold above basal levels [9].

Chemical compound and disease context of P2RY2

• Therefore, we cloned and expressed the P2Y6 and P2Y4 receptors in 1321N1 human astrocytoma cells and compared their relative selectivities for UDP, UTP, and other uridine and adenine nucleotides with that of the P2Y2 receptor expressed in the same cells [10].
• The P2Y2 receptor agonists diuridine tetraphosphate (diquafosol) and the uracil-cytosine dinucleotide denufosol are currently undergoing clinical trials for dry eye disease, retinal detachment disease, upper respiratory tract symptoms, and cystic fibrosis, respectively [11].
• 3. Human 1321N1 astrocytoma cells stably expressing the phospholipase C-coupled human P2U-purinoceptor were utilized to test the activity of UTP gamma S. UTP gamma S (EC50 = 240 nM) was essentially equipotent to UTP and ATP for stimulation of inositol phosphate formation [12].
• Finally, sumatriptan synergistically enhanced P2U purinoceptor stimulated [3H]inositol phosphate accumulation through a pertussis toxin-sensitive mechanism [13].
• Growth inhibition and apoptosis induced by P2Y2 receptors in human colorectal carcinoma cells: involvement of intracellular calcium and cyclic adenosine monophosphate [14].

Biological context of P2RY2

• An increase in cell number was caused by low doses of the nonspecific P2 receptor agonist ATP, the P2Y2 receptor agonist UTP (p<0.001), and the P2Y1 receptor agonist 2MeSADP (p<0.05) [15].
• These data demonstrate that multiple P2Y receptors (P2Y1, P2Y2, and P2Y4 subtypes) are differentially involved in the regulation of proliferation in human keratinocytes and therefore may be important in wound healing [16].
• ATP, at high concentrations, induced apoptosis through ligation of P2X7 and P2Y1 receptors; conversely, ATP, at lower concentrations, and UTP stimulated proliferation, probably acting via P2Y2 receptors [17].
• We have recently cloned from the human genome a new subtype of receptor (tentatively called P2Y4), which is structurally related to the P2U receptor [18].
• Photolabeling of the 53-kDa protein by [alpha-32P]BzATP was inhibited by ATP but not by UTP, raising the possibility that the P2U receptor may have distinct binding sites for each nucleotide [19].

Anatomical context of P2RY2

• In this study, we addressed the hypothesis that activation of P2Y2 receptors by extracellular nucleotides modulates the expression of adhesion molecules on vascular endothelial cells that are important for monocyte recruitment [1].
• The P2Y2 nucleotide receptor mediates UTP-induced vascular cell adhesion molecule-1 expression in coronary artery endothelial cells [1].
• Extracellular nucleotides are agonists at the family of receptors known as the P2 receptors, and in keratinocytes the P2Y2 subtype is known to elevate the intracellular free calcium concentration (Cai) and stimulate proliferation [16].
• P2Y2 receptors were found only in periderm cells and may have a role in chloride and fluid secretion into the amniotic fluid [20].
• These experiments revealed that P2Y2 and P2Y6 mRNA are co-expressed in the IHAEo-, 16HBE14o- and A549 epithelial cell lines [21].

Associations of P2RY2 with chemical compounds

• The P2Y2-receptor is activated by UTP and ATP and blocked by suramin [22].
• In both cell types, adenosine 5'-triphosphate and uridine 5'-triphosphate induced Cai transients of approximately equal duration, magnitude, and shape, confirming the presence of functional P2Y2 receptors [16].
• 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 [21].
• Applications with ATP and UTP revealed that luminal membranes of NHNE cells express P2Y2 and P2Y6 receptors and basolateral membranes express P2Y2 receptor [23].
• For example, the dinucleotide INS 37217 (Up4dC) potently activates the P2Y2 receptor, and the non-nucleotide antagonist A-317491 is selective for P2X(2/3)/P2X3 receptors [24].
• Collectively, these results suggest that alpha v integrin complexes provide the P2Y2R with access to G12, thereby allowing activation of this heterotrimeric G protein that controls actin cytoskeletal rearrangements required for chemotaxis [25].

Physical interactions of P2RY2

• Here it is demonstrated that activation of the G protein-coupled P2Y2 receptor (P2Y2R) subtype expressed in human 1321N1 astrocytoma cells enhanced the release of sAPP alpha in a time- and dose-dependent manner [26].

Regulatory relationships of P2RY2

• P2Y2 antisense oligonucleotides inhibited VCAM-1 expression induced by UTP but not by tumor necrosis factor-alpha [1].
• P2Y2 nucleotide receptors enhance alpha-secretase-dependent amyloid precursor protein processing [26].
• Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor [27].
• Taken together, our results show that endogenous P2Y2 receptor activation downregulates CFTR activity in a cAMP-independent manner in CHO cells [28].
• G(alpha16) is obligatory for P2Y2 receptor-dependent Ca2+-mobilization in human erythroleukemia cells and induces hematopoietic cell differentiation [29].

Other interactions of P2RY2

• Human keratinocytes express multiple P2Y-receptors: evidence for functional P2Y1, P2Y2, and P2Y4 receptors [16].
• The P2X7 receptor agonist benzoylbenzoyl-adenosine 5'-triphosphate and high concentrations of adenosine 5'-triphosphate (1000-5000 microM) caused a significant reduction in A431 cell number (p<0.001), whereas the P2Y2 receptor agonist uridine 5'-triphosphate caused a significant amount of proliferation (p<0.001) [2].
• Expressions of P2Y2 and P2Y6 receptors in NHNE cells were further verified by immunoblotting using specific antibodies [23].
• In conclusion, P2X1, P2Y2, and P2Y6 are the most expressed P2 receptors in SMC and are thus probably mediating the contractile and mitogenic actions of extracellular nucleotides [30].
• CONCLUSION: This study showed that P2Y2 and P2Y11 receptors were expressed in NHNE cells and that their agonists, UTP and ATPgammaS, act as secretogogues on mucin secretion via Ca2+-dependent pathways [31].

Analytical, diagnostic and therapeutic context of P2RY2

• The present study was designed to examine the expression and regulation of the P2UR in human granulosa-luteal cells (hGLCs) by RT-PCR and Northern blot analysis [32].
• A PCR product corresponding to the expected 599-bp P2UR complementary DNA was obtained from hGLCs [32].
• Purification of HA-tagged P2Y2 receptors from transfected human 1321N1 astrocytoma cells yielded a protein with a molecular size determined by SDS-PAGE to be in the range of 57-76 kDa, which is typical of membrane glycoproteins with heterogeneous complex glycosylation [33].
• Microfluorometry and confocal laser scanning was used on preparations stained with the Ca2+-sensitive dyes Calcium Green-1 and Fura Red. In myelinating Schwann cells of human and rat nerves, the ATP-induced rise of [Ca2+]i resulted from the activation of a P2Y2 purinoceptor subtype (rank order of potency: UTP > or = ATP >> 2-MeSATP = ADP) [34].
• Flow cytometry analysis of thymocyte subsets excluded the possibility that the observed increases in P2Y2 receptor mRNA expression were due to the enrichment of steroid-treated cells with an P2Y2 mRNA-rich thymocyte subset [35].

References