Affinage

P2RY6

P2Y purinoceptor 6 · UniProt Q15077

Audit flag: ungrounded claim
Length
328 aa
Mass
36.4 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P2RY6 (P2Y6) is a pyrimidinergic G protein-coupled receptor selectively activated by UDP that couples to Gq/phospholipase C to drive IP3/Ca2+ signaling, and engages additional G protein outputs to regulate inflammation, tissue remodeling, and phagocytosis across many cell types (PMID:8670200, PMID:9226417, PMID:18523137). UDP/P2Y6 stimulation activates downstream cascades including RhoA-Rho kinase-driven actin reorganization (PMID:10843869), PKC-ERK and Src-p38-NF-κB modules that promote cell survival and chemokine output (CCL2, CCL3, CXCL8) (PMID:12825835, PMID:22095787, PMID:21317391, PMID:23916475), and NFAT and AP-1 transcriptional programs (PMID:22095787, PMID:21317391). Beyond UDP, P2Y6 is activated by the COX-2 product PGE2-glyceryl ester (PMID:28539604) and by long-chain ceramides that trigger Gq/NLRP3 inflammasome signaling to aggravate atherosclerosis (PMID:40049228). In the CNS, microglial P2Y6 senses UDP leaked from damaged neurons and drives phagocytosis—both clearance of debris and phagoptosis of stressed-but-viable neurons—through Rac1/MLCK signaling, lysosome biogenesis, and NF-κB-dependent cytokine production, contributing to neuronal and memory loss in amyloid-β and tau models and to neuronal engulfment in epilepsy and stroke (PMID:17410128, PMID:24838858, PMID:32154670, PMID:34965424, PMID:38614103). In the vasculature and heart, P2Y6 couples through Gα12/13 to mediate myogenic tone, pressure-overload cardiac fibrosis, and—via stable heterodimerization with the angiotensin II receptor AT1R—a shift toward G protein-dependent hypertrophy that promotes hypertension (PMID:19008857, PMID:26787451, PMID:27255725). P2Y6 also regulates metabolic physiology, promoting AgRP neuron-driven feeding, insulin secretion, and tissue-specific glucose handling (PMID:25249240, PMID:26359991, PMID:33199639). Unlike the rapidly recycling P2Y4, P2Y6 desensitizes slowly (PMID:9226417, PMID:11114308) and undergoes a distinct β-arrestin-independent redox-dependent internalization in which electrophiles covalently modify Cys220 to drive Lys137 ubiquitylation, degradation, and control of intestinal inflammation (PMID:35015570).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Establishing the identity and pharmacology of an orphan-like P2Y receptor defined P2Y6 as a UDP-preferring, Gq-coupled pyrimidinergic receptor distinct from ATP-responsive subtypes.

    Evidence Cloning from placenta cDNA and IP3 accumulation in stably expressing 1321N1 cells with defined agonist rank order

    PMID:8670200

    Open questions at the time
    • Endogenous ligand identity beyond UDP not addressed
    • No structural basis for nucleotide selectivity
  2. 1997 High

    Characterizing desensitization kinetics revealed that P2Y6 signaling is unusually slow and sustained, distinguishing it functionally from related P2Y4.

    Evidence IP3 assays with pertussis toxin treatment in P2Y6-expressing 1321N1 cells

    PMID:9226417

    Open questions at the time
    • Molecular basis of slow desensitization not resolved here
  3. 1999 High

    Reconstitution in neurons showed P2Y6 is not strictly Gq-restricted but exhibits dual G-protein coupling, modulating ion channels through both PTX-sensitive and PTX-resistant pathways.

    Evidence cRNA microinjection and voltage clamp in rat sympathetic neurons with PTX dissection

    PMID:10193782

    Open questions at the time
    • Native neuronal relevance of recombinant coupling not established
    • Specific Gα subunits not identified
  4. 2000 Medium

    Identifying RhoA/Rho-kinase activation and defining the structural determinants of internalization explained both P2Y6's cytoskeletal effects and its resistance to rapid desensitization.

    Evidence Membrane fractionation, dominant-negative RhoA, and phosphorylation/truncation mutagenesis in transfected cells

    PMID:10843869 PMID:11114308

    Open questions at the time
    • Internalization mechanism characterized by comparison to P2Y4 in single study
    • G protein linking P2Y6 to RhoA not defined
  5. 2003 High

    Demonstrating UDP/P2Y6 anti-apoptotic and dual Ca2+/cAMP signaling extended the receptor's outputs to cell survival and epithelial secretion beyond canonical PLC/Ca2+.

    Evidence PKC/ERK pathway dissection in astrocytoma; Ussing chamber and Xenopus oocyte CFTR co-expression

    PMID:12569163 PMID:12825835

    Open questions at the time
    • Mechanism of cAMP elevation by a Gq-coupled receptor unresolved
    • PKC isotype specificity inferred pharmacologically
  6. 2004 High

    Development of selective insurmountable antagonists (MRS2578/MRS2567) provided the gold-standard tools that enabled subsequent loss-of-function dissection in native systems.

    Evidence PLC/IP3 inhibition curves across a P2Y selectivity panel in 1321N1 cells

    PMID:15081875

    Open questions at the time
    • Off-target effects at high concentrations not fully excluded
  7. 2008 High

    Genetic knockout confirmed P2Y6 is the sole macrophage UDP receptor and defined its non-redundant roles in macrophage, endothelial, and smooth muscle responses, validating receptor specificity.

    Evidence P2Y6 gene-targeted mice with inositol phosphate assays and aortic ring contractility

    PMID:18523137

    Open questions at the time
    • Cell-autonomous versus systemic contributions not separated
  8. 2007 High

    Discovery that microglial P2Y6 senses neuronally leaked UDP to trigger phagocytosis established the receptor as a 'find/eat-me' sensor in CNS injury.

    Evidence Microsphere phagocytosis with MRS2578 plus kainic acid in vivo injury model

    PMID:17410128

    Open questions at the time
    • Downstream phagocytic machinery not yet defined
    • Distinction between debris clearance and viable-cell engulfment not made
  9. 2008 High

    Linking P2Y6 to Gα12/13 in cardiomyocytes connected mechanical-stress nucleotide release to fibrogenic gene programs, defining a pathological cardiac remodeling axis.

    Evidence Transgenic Gα12/13 inhibitory peptides, pannexin inhibition, and pressure overload model

    PMID:19008857

    Open questions at the time
    • Relative contribution of Gα12/13 versus Gq in vivo not quantified
  10. 2011 High

    Defining NFAT- and AP-1-driven chemokine programs placed P2Y6 upstream of specific transcription factors governing leukocyte recruitment in glia and epithelium.

    Evidence siRNA/antagonist plus reporter mutagenesis, ChIP, and transmigration assays

    PMID:21317391 PMID:22095787

    Open questions at the time
    • In vivo necessity of each transcription factor downstream of P2Y6 not isolated
  11. 2013 High

    Identifying PI(4,5)P2 hydrolysis-mediated crosstalk with P2X4 and pannexin-1-dependent ATP release revealed how P2Y6 integrates with other purinergic signaling to shape microglial and urothelial responses.

    Evidence Patch clamp, YO-PRO-1 uptake, PI(4,5)P2 manipulation, and in vivo urodynamics with co-localization

    PMID:24123515 PMID:24269631

    Open questions at the time
    • Physiological setting where P2Y6-P2X4 crosstalk dominates not defined
  12. 2014 High

    Demonstrating that UDP/P2Y6 is necessary and sufficient for phagoptosis of viable neurons reframed P2Y6-driven microglial phagocytosis as a driver of neuronal loss, not just debris clearance.

    Evidence Multiple inflammatory stimuli with antagonist/apyrase in mixed cultures and in vivo LPS striatal injection

    PMID:24838858

    Open questions at the time
    • Signals marking neurons as viable phagoptosis targets not fully defined
  13. 2016 High

    Discovery of stable P2Y6R-AT1R heterodimers and a requirement for P2Y6 in myogenic tone explained an age-dependent signaling switch toward G protein-dependent vascular hypertrophy and hypertension.

    Evidence Co-IP, P2Y6 KO mice, blood pressure and β-arrestin assays; arteriography in P2ry6-/- mice with hemichannel and RhoA readouts

    PMID:26787451 PMID:27255725

    Open questions at the time
    • Structural basis of the heterodimer interface unknown
    • Generality of the AT1R switch across vascular beds not established
  14. 2017 High

    Deorphanizing P2Y6 toward PGE2-glyceryl ester showed the receptor responds to a lipid agonist with far higher potency than UDP, broadening its ligand repertoire beyond nucleotides.

    Evidence RNA-seq subtractive screen with Ca2+/IP1 assays in heterologous and endogenous systems

    PMID:28539604

    Open questions at the time
    • Physiological contexts where PGE2-G versus UDP dominate not delineated
  15. 2018 High

    Linking P2Y6 to AKT-mediated XIAP stabilization defined a pro-survival, chemoresistance-promoting role in colorectal tumorigenesis.

    Evidence P2ry6-/- mice in AOM/DSS model with XIAP/AKT biochemistry and 5-FU resistance assays

    PMID:29454075

    Open questions at the time
    • Whether tumor effect is microglial/immune or epithelial-cell-intrinsic not fully resolved
  16. 2020 High

    Tissue-specific knockouts and stroke models resolved P2Y6's divergent metabolic and phagocytic roles, including opposing outcomes in adipose versus muscle and beneficial phagocytosis in ischemia.

    Evidence Adipocyte- and muscle-specific conditional KO metabolic phenotyping; tMCAO with Rac1/MLCK readouts

    PMID:32154670 PMID:33199639

    Open questions at the time
    • Stroke study relies on pharmacology in single lab
    • Reconciliation of beneficial (stroke) versus detrimental (neurodegeneration) phagocytosis not mechanistically settled
  17. 2021 High

    Genetic demonstration that microglial P2Y6 drives amyloid-β- and tau-induced neuronal and memory loss via live-cell phagocytosis positioned the receptor as a disease-relevant phagoptosis effector.

    Evidence P2Y6R KO in Aβ injection and P301S TAU models with memory testing and live-versus-dead target phagocytosis assays

    PMID:34965424

    Open questions at the time
    • Therapeutic window for inhibition versus loss of protective clearance not defined
  18. 2022 High

    Identifying redox-dependent alternative internalization (REDAI) via Cys220 covalent modification and Lys137 ubiquitylation revealed a β-arrestin-independent regulatory mechanism controlling receptor levels and intestinal inflammation.

    Evidence Cys220Ser mutagenesis, ubiquitylation/internalization assays, and Cys220Ser knock-in mice in DSS colitis

    PMID:35015570

    Open questions at the time
    • Endogenous electrophiles driving physiological REDAI not fully cataloged
    • Ubiquitin ligase mediating Lys137 ubiquitylation not identified
  19. 2024 High

    Direct in vivo UDP imaging tied microglial P2Y6 calcium activity to lysosome biogenesis and NF-κB cytokine output during epileptogenesis, mechanistically connecting seizure-released UDP to neuronal engulfment.

    Evidence GRABUDP1.0 biosensor, P2Y6 KO, and CalEx calcium-extrusion approach with cognitive testing

    PMID:38614103

    Open questions at the time
    • Translation to human epilepsy not established
  20. 2025 Medium

    Identifying long-chain ceramides as P2Y6 agonists that trigger Gq/NLRP3 inflammasome signaling extended the receptor's role to lipid sensing in atherosclerosis.

    Evidence Systematic GPCR/NLRP3 screen with P2Y6R genetic/pharmacological inhibition in atherosclerosis models

    PMID:40049228

    Open questions at the time
    • Structural ceramide-binding data were obtained for CYSLTR2, not P2Y6R directly
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct ligands (UDP, PGE2-G, ceramides) and G-protein outputs (Gq, Gα12/13, Gi) are selected to produce context-specific outcomes—and how protective versus pathological phagocytosis is determined—remains unresolved.
  • No structural model of human P2Y6 with its endogenous ligands
  • Ligand-biased signaling rules not defined
  • Determinants distinguishing beneficial from harmful microglial phagocytosis unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 2
Partners
AGTR1P2RX4P2RY4
Complex memberships
P2Y6-P2Y4 hetero-oligomerP2Y6R-AT1R heterodimer

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Human P2Y6 receptor, cloned from placenta cDNA library, is a Gq-coupled GPCR that stimulates IP3 formation in response to UDP (most potent), with agonist rank order: UDP > 5-bromo-UTP > UTP > ADP > 2-methylthio-ATP >> ATP, establishing it as a pyrimidinergic receptor. Stable expression in 1321N1 cells, IP3 accumulation assay Biochemical and biophysical research communications High 8670200
1997 P2Y6 receptor activates IP3 production via a pertussis toxin-insensitive G-protein (Gq) and displays markedly slow desensitization compared to P2Y4: maximal IP3 response takes ~15 min and is maintained for ≥3 h; full second response is obtained after 45 min but lost after 165 min. IP3 accumulation assay in P2Y6-expressing 1321N1 cells; pertussis toxin treatment European journal of pharmacology High 9226417
1999 Heterologously expressed rat P2Y6 receptor couples to N-type Ca2+ channels (inhibition ~53–73%) and M-type K+ channels (inhibition up to 71%) in rat sympathetic neurons; N-type Ca2+ channel inhibition is partially PTX-sensitive (via Gi/Go) whereas M-type K+ channel inhibition is PTX-resistant, demonstrating dual G-protein coupling. cRNA microinjection into rat sympathetic neurons; whole-cell and perforated-patch voltage clamp; pertussis toxin treatment British journal of pharmacology High 10193782
2000 P2Y6 receptor stimulation causes translocation of RhoA to the membrane and activates Rho kinase-dependent actin stress fiber formation in aortic myocytes and Swiss 3T3 cells transfected with P2Y6; this is blocked by C3 exoenzyme and the Rho kinase inhibitor Y-27632, and by dominant-negative RhoA. Transfection of P2Y6 into Swiss 3T3 cells; membrane fractionation for RhoA; phalloidin staining for actin; dominant-negative RhoA and pharmacological inhibitors American journal of physiology. Heart and circulatory physiology High 10843869
2000 P2Y6 receptor undergoes slow agonist-dependent loss of cell surface receptors that does not recover rapidly after UDP removal (unlike P2Y4 which rapidly recycles); PKC and Ca2+-activated kinases are not involved. C-terminal Ser-333/Ser-334 of P2Y4 mediate rapid phosphorylation/desensitization/internalization — equivalent determinants absent in P2Y6 explain its resistance. Radioligand binding for surface receptor quantification; [32P]-phosphorylation of wild-type and truncation/point mutants; flow cytometry The Journal of biological chemistry Medium 11114308
2002 UDP acting on P2Y6 receptor promotes vascular smooth muscle cell mitogenesis (DNA and protein synthesis, cell cycle S/G2 progression) via phospholipase C, possibly PKC-δ, and a tyrosine kinase pathway, independent of Gi, eicosanoids, and PKA. [3H]-thymidine and [3H]-leucine incorporation; flow cytometry; selective P2Y6 agonist UDPβS; pharmacological inhibitors; hexokinase control to exclude UDP→UTP conversion American journal of physiology. Heart and circulatory physiology High 11788430
2003 P2Y6 receptor activation by UDP protects 1321N1 astrocytoma cells against TNFα-induced apoptosis by activating PKCα, PKCε, and PKCζ isotypes and ERK1/2; this is partially blocked by PKC inhibitors (GF109203X, Gö6976) and ERK inhibitors (PD98059, U0126), but not by Akt inhibition or calcium chelation. Flow cytometry for apoptosis; PKC isotype activation assays; pharmacological kinase inhibitors; ERK phosphorylation assays Cellular and molecular neurobiology Medium 12825835
2003 Basolateral P2Y6 receptor in colonic epithelium stimulates sustained Cl- secretion via both Ca2+ and cAMP; in Xenopus oocytes co-expressing P2Y6 and CFTR, UDP activates first a transient Ca2+-activated Cl- current and subsequently CFTR current, establishing P2Y6 as a receptor able to elevate both [Ca2+]i and cAMP. Ussing chamber electrophysiology; cAMP assay in colonic crypts; Xenopus oocyte two-electrode voltage clamp co-expressing P2Y6 + CFTR; RT-PCR and immunohistochemistry The Journal of clinical investigation High 12569163
2004 Diisothiocyanate derivatives MRS2567 and MRS2578 are potent, insurmountable antagonists selective for P2Y6 over P2Y1, P2Y2, P2Y4, and P2Y11 receptors (IC50 of MRS2578 ~37 nM at human P2Y6); at 1 µM, they completely block UDP-mediated protection from TNFα-induced apoptosis. PLC/IP3 assay in recombinant P2Y receptor-expressing 1321N1 cells; concentration-response inhibition curves; apoptosis assay Biochemical pharmacology High 15081875
2005 P2Y6 receptor activation by UDP or the selective agonist INS48823 activates NF-κB (p65 nuclear translocation) in osteoclasts via a proteasome-dependent pathway, and enhances osteoclast survival; this effect is direct (not dependent on RANK ligand) and blocked by the NF-κB inhibitor SN50. Immunofluorescence for NF-κB p65; RT-PCR in purified osteoclasts; calcium imaging; cell survival assay; SN50 peptide inhibitor; osteoprotegerin control The Journal of biological chemistry High 15722352
2005 HNP (human neutrophil peptide)-induced IL-8 production in lung epithelial cells is mediated predominantly through the P2Y6 signaling pathway, as shown by antisense oligonucleotide knockdown of specific P2Y receptor subtypes. Antisense oligonucleotide knockdown of P2Y receptors; ELISA for IL-8; comparison with UDP and ATP stimulation Blood Medium 16322472
2006 P2Y6 receptor mediates positive inotropy in cardiomyocytes via a phospholipase C/IP3 pathway: the selective agonist UDPβS increases cardiomyocyte contraction by 35%, and this is abolished by the P2Y6 blocker MRS2578 and the PLC inhibitor U73122. Electrically stimulated isolated mouse cardiomyocytes; contraction measurement; pharmacological inhibitors; Western blot and immunohistochemistry for receptor expression Circulation research High 16543499
2007 UDP acting on microglial P2Y6 receptor triggers phagocytosis of microspheres in a concentration-dependent, P2Y6-dependent manner; P2Y6 mRNA is upregulated in activated microglia after kainic acid-induced neuronal damage; leaked UDP from damaged neurons acts as the endogenous signal. Microsphere uptake assay; selective antagonist MRS2578; kainic acid in vivo model; RT-PCR and in situ hybridization Nature High 17410128
2007 P2Y6 and P2Y4 receptors form high-order oligomeric complexes (up to dimers) in native neuronal phenotypes; P2Y6 exists as both dimers and monomers in lipid rafts of synaptosomes; UDP ligand activation shifts P2Y6 oligomerization state, whereas P2Y4 is unaffected; in PC12 cells, endogenous P2Y4 forms hetero-oligomers specifically with P2Y6. Blue Native PAGE; SDS-PAGE; co-immunoprecipitation; sucrose gradient fractionation of lipid rafts; synaptosome preparations Biochimica et biophysica acta Medium 17481575
2008 P2Y6 receptor signaling through Gα12/13 in cardiomyocytes triggers pressure overload-induced cardiac fibrosis: mechanical stretch causes ATP/UDP release via pannexin hemichannels, which activates P2Y6 receptors, inducing expression of fibrogenic genes (TGF-β, CTGF, periostin) and ACE upstream of the Ang II–TGF-β pathway. Transgenic expression of Gα12/13 inhibitory polypeptides; pressure overload model; pannexin hemichannel inhibition; P2Y6 receptor antagonism; gene expression analysis The EMBO journal High 19008857
2008 P2Y6 knockout mice lack UDP-stimulated inositol phosphate production in macrophages (confirming P2Y6 is the sole UDP receptor on macrophages), lack UDP-induced endothelium-dependent aortic relaxation, and lack UDP-induced vasoconstriction when eNOS is blocked, demonstrating distinct roles in macrophages, endothelial cells, and vascular smooth muscle. P2Y6 gene-targeted knockout mice; inositol phosphate assay in macrophages; aortic ring contractility; cytokine ELISA (IL-6, MIP-2, TNF-α) Molecular pharmacology High 18523137
2008 P2Y6 receptor activation by UDP stimulates insulin secretion from pancreatic beta-cells in a glucose-dependent manner via a P2Y6-specific mechanism, blocked by MRS2578; P2Y6 is the dominant pyrimidine receptor expressed in islets and purified beta-cells. Real-time PCR; insulin/glucagon secretion assay from isolated mouse islets and purified beta-cells; selective agonist UDPβS and antagonist MRS2578 Biochemical and biophysical research communications Medium 18387359
2009 P2Y6 receptors on mast cells cooperate with CysLT1R through reciprocal ligand-mediated cross-talk: P2Y6 antagonist MRS2578 blocks ERK activation and survival responses to both UDP and LTD4; both responses are absent in cells lacking CysLT1R or LTC4 synthase, indicating P2Y6 requires an intact cys-LT autocrine loop for its survival/activation signaling. ERK phosphorylation assay; mast cell survival assay; selective antagonist MRS2578; CysLT1R-knockout and LTC4 synthase-knockout cells; shRNA knockdown Journal of immunology High 19124756
2010 UDP/P2Y6 signaling in intestinal epithelial cells induces CXCL8 expression via the PKCδ–MEK1/2–ERK1/2–c-fos/c-jun (AP-1) pathway; mutation of the AP-1 site in the CXCL8 promoter abolishes the UDP-stimulating effect; UDP enemas increase neutrophil recruitment to inflamed mouse mucosa. Luciferase reporter (AP-1 site mutant); chromatin immunoprecipitation (ChIP); Western blot for phosphorylation; qPCR; pharmacological inhibitors; in vivo colitis model + immunofluorescence Inflammatory bowel diseases High 22095787
2011 UDP/P2Y6 activation of microglia and astrocytes induces CCL2 and CCL3 expression via Gq/PLC/calcium-dependent pathway activating NFATc1/c2 transcription factors; calcineurin inhibition and NFAT inhibitors reduce UDP-induced chemokine synthesis; UDP-treated astrocytes recruit monocytes in transmigration assay. siRNA knockdown of P2Y6; selective antagonist MRS2578; PLC inhibitor; NFAT inhibitors/calcineurin inhibitor; ELISA; RT-PCR; transmigration assay Journal of immunology High 21317391
2011 P2Y6 receptor stimulation by extracellular UDP promotes bone resorption: it stimulates osteoclast formation from precursors and enhances mature osteoclast resorptive activity; P2Y6R-/- mice have increased bone mineral content, cortical bone volume, and cortical thickness, with decreased osteoclast surface. P2Y6 knockout mice; osteoclast resorption pit assay; DEXA scanning; microcomputed tomography; histomorphometry Endocrinology High 21828185
2013 P2Y6 receptor activation of PLC mediates hydrolysis of PI(4,5)P2, which inhibits P2X4 channel function in microglia: P2Y6 activation reduces P2X4-mediated Ca2+ entry, current amplitude, activation/desensitization rates, and large-conductance pore dilation (YO-PRO-1 uptake); PI(4,5)P2 depletion underlies this crosstalk; P2Y6 also modulates ATP-dependent microglial migration. Calcium imaging; YO-PRO-1 uptake assay; whole-cell patch clamp in recombinant systems; PI(4,5)P2 manipulation; primary microglia and LPS-activated microglia; migration assay Glia High 24123515
2013 P2Y6 receptor activation causes bladder overactivity by releasing ATP from the urothelium via pannexin-1 hemichannels; P2Y6 and pannexin-1 co-localize in the urothelium; P2Y6 agonist-induced bladder hyperactivity and ATP release are blocked by pannexin-1 hemichannel inhibitors (10Panx, carbenoxolone) but not systemic routes, establishing a luminal paracrine mechanism. In vivo urodynamics in anesthetized rats; propidium iodide hemichannel permeability assay; confocal co-localization; ATP bioluminescence; selective P2Y6 agonist PSB0474 and antagonist MRS2578 Biochemical pharmacology High 24269631
2013 P2Y6 receptor activation in spinal microglia induces CCL2 production via a PLC→Src tyrosine kinase→ERK1/2 and p38 MAPK→NF-κB pathway; selective P2Y6 antagonist MRS2578 blocks CCL2, and UTP effect is not blocked by P2Y2 siRNA, confirming P2Y6 mediates this response. Primary spinal microglia cultures; ELISA and RT-PCR for CCL2; selective P2Y6 antagonist MRS2578; P2Y2 siRNA knockdown; kinase inhibitors (U0126, SB202190, U73122, PP2); NF-κB assay Neuropharmacology High 23916475
2014 Blocking UDP/P2Y6 signaling (with apyrase, Reactive Blue 2, or MRS2578) prevents microglial phagocytosis of viable neurons (phagoptosis) induced by LPS, lipoteichoic acid, amyloid-β, peroxynitrite, or reactive nitrogen species, and prevents neuronal loss; UDP alone is sufficient to stimulate microglial phagocytosis and cause neuronal loss reversible by microglial elimination. Mixed neuronal/glial cultures; neuronal viability assay; selective P2Y6 antagonist MRS2578; apyrase; in vivo LPS injection into rat striatum with MRS2578 treatment Glia High 24838858
2014 P2Y6 receptor activation in microglia induces NO release via the PLC-PKC-iNOS pathway, which causes apoptosis in neighboring astrocytes but not microglia; this limits astrocyte proliferation and prevents excessive astrogliosis in LPS-treated microglia-astrocyte co-cultures. Co-cultures of microglia and astrocytes; Griess reaction for NO; TUNEL/Hoechst staining; Western blot and immunofluorescence for P2Y6 and iNOS; PLC, PKC, and NOS inhibitors; selective P2Y6 agonist PSB0474 and antagonist MRS2578 Journal of neuroinflammation Medium 25178395
2014 P2Y6 receptor activation in spinal microglia (but not astrocytes) contributes to neuropathic pain maintenance; minocycline (microglial inhibitor) reduces P2Y6 upregulation but fluorocitrate (astrocyte inhibitor) does not, placing P2Y6 specifically in spinal microglia in this pain pathway. Spinal nerve ligation model in rats; intrathecal antagonist administration (MRS2578); minocycline and fluorocitrate treatment; Iba-1/GFAP immunostaining; Western blot for P2Y6 Molecular pain Medium 24886406
2014 P2Y6 receptor promotes glucose uptake in skeletal muscle and adipocytes via AMPK phosphorylation, GLUT4 membrane recruitment, and HDAC5 signaling; P2Y6R-knockout adipocytes show no increase in glucose uptake upon P2Y6 agonist treatment; AMPK siRNA or Compound C abolishes P2Y6-mediated glucose uptake. [3H]2-deoxyglucose uptake assay; GLUT4 membrane recruitment assay; AMPK phosphorylation (Western blot); AMPK siRNA; P2Y6R-KO adipocytes; selective agonist MRS2957 and antagonist MRS2578 PloS one High 25249240
2015 AgRP neurons in the arcuate nucleus express P2Y6 receptor; central UDP application promotes AgRP neuron action potential firing, ERK phosphorylation, and cFos expression; central UDP promotes feeding, which is abrogated by P2Y6 knockout or pharmacogenetic inhibition of AgRP neurons; hypothalamic UDP is elevated in obese animals due to increased circulating uridine. Brain slice electrophysiology; in vivo ERK/cFos assays; intracerebroventricular UDP injection; P2Y6 KO mice; AgRP-specific pharmacogenetics (DREADDs); obese mouse model metabolomics Cell High 26359991
2016 P2Y6R and AT1R form stable heterodimers that enhance G protein-dependent (Gα-q/12/13) vascular hypertrophy signaling while reducing β-arrestin-dependent AT1R internalization; P2Y6R expression increases with age in vascular smooth muscle cells, converting AT1R signaling from β-arrestin-dependent proliferation to G protein-dependent hypertrophy; MRS2578 disrupts heterodimers and suppresses Ang II-induced hypertension. Co-immunoprecipitation for heterodimer formation; P2Y6R KO mice; blood pressure measurement; vascular remodeling assays; β-arrestin assay; age-dependent expression analysis; pharmacological disruption with MRS2578 Science signaling High 26787451
2016 P2Y6 receptor is essential for myogenic tone (MT) of resistance arteries: P2Y6 activation is mandatory for RhoA-GTP binding, myosin light chain, p42/44, and JNK phosphorylation in arterial smooth muscle cells; MT is abrogated by P2Y6 blockade and absent in P2ry6-/- arteries; nucleotide release through hemichannels (Cx43, P2X7) triggers autocrine P2Y6 signaling upon pressure. Arteriography of mesenteric arteries; P2ry6-/- mice; hemichannel inhibitors; Cx43+/- and P2rx7-/- mice; RhoA-GTP pulldown; phosphorylation assays; myocardial infarction model Arteriosclerosis, thrombosis, and vascular biology High 27255725
2017 Prostaglandin E2 glyceryl ester (PGE2-G), a COX-2 product of 2-arachidonoylglycerol, is an endogenous agonist of P2Y6 receptor with an EC50 of ~1 pM (vs ~50 nM for UDP), identified via transcriptome-wide RNA-seq subtractive screening and validated in heterologous and endogenous expression systems with multiple functional readouts. RNA-seq subtractive screening of responder vs non-responder cell lines; Ca2+ mobilization assay; IP1 assay; heterologous P2Y6 expression; endogenous system validation Scientific reports High 28539604
2018 P2Y6 receptor promotes colorectal tumor cell survival by stabilizing XIAP via AKT-mediated phosphorylation, thereby inhibiting apoptosis and contributing to chemoresistance to 5-fluorouracil; P2ry6-/- mice develop fewer and smaller colorectal tumors after AOM/DSS challenge. P2ry6-/- mice in AOM/DSS CRC model; HT29 cell apoptosis assay; Western blot for XIAP phosphorylation and AKT activation; tumoroids from CRC; MRS2693 selective agonist; 5-FU resistance assay Biochimica et biophysica acta. Molecular basis of disease High 29454075
2020 P2Y6 receptor mediates phagocytosis by microglia via Rac1 and MLCK signaling: P2Y6 inhibition decreases Rac1-pRAC1 and MLCK expression after ischemic stroke; P2Y6-mediated phagocytosis is beneficial in ischemic stroke (P2Y6 inhibition aggravates brain atrophy and neurological deficits). Transient middle cerebral artery occlusion model; MRS2578 treatment; neurological scoring; Western blot for Rac1 and MLCK; brain volume measurement CNS neuroscience & therapeutics Medium 32154670
2020 Adipocyte-specific P2Y6R deletion protects mice from diet-induced obesity and improves glucose tolerance via reduced JNK signaling, enhanced PPARα activity and downstream PGC1α, and beiging of white adipose tissue; skeletal muscle-specific P2Y6R deletion reduces glucose uptake, impairing glucose homeostasis. Conditional adipocyte-specific and skeletal muscle-specific P2Y6R KO mice; metabolic phenotyping; RNA-seq; Western blot for JNK, PPARα, PGC1α; whole-body KO comparison Proceedings of the National Academy of Sciences High 33199639
2021 Microglial P2Y6R mediates tau- and amyloid-β-induced neuronal and memory loss via phagocytosis of neurons: P2Y6R KO prevents Aβ-injection-induced microglial neuronal phagocytosis, neuronal loss, and memory loss in vivo; in P301S TAU mice, P2Y6R KO prevents TAU-induced neuronal and memory loss; in vitro, P2Y6R KO blocks microglial phagocytosis of live but not dead targets. P2Y6R KO mice; intracerebral Aβ injection; P301S TAU transgenic model; memory testing; in vitro phagocytosis of live vs dead targets; glial-neuronal co-cultures Cell reports High 34965424
2022 P2Y6 receptor undergoes redox-dependent alternative internalization (REDAI) independent of β-arrestin: electrophilic isothiocyanate compounds covalently modify Cys220 of P2Y6R, promoting ubiquitylation of Lys137 and receptor internalization and degradation; endogenous electrophiles also promote this pathway; Cys220Ser mutant P2Y6R mice show increased colitis susceptibility, linking REDAI to intestinal inflammation control. Site-directed mutagenesis (Cys220Ser); ubiquitylation assay; internalization/degradation assays in multiple cell lines; Cys220Ser knock-in mice in DSS colitis model; covalent modification assay Science signaling High 35015570
2024 Microglial P2Y6 receptor mediates calcium signaling in epileptogenesis by sensing UDP released during seizures (detected with novel GRABUDP1.0 fluorescent sensor); P2Y6 calcium activity drives lysosome biogenesis and NF-κB-related cytokine production; P2Y6 KO prevents microglia from fully engulfing neurons and attenuates CA3 neuron loss and cognitive deficits in epilepsy; calcium extruder ('CalEx') expression recapitulates P2Y6 KO phenotypes. Novel UDP fluorescent sensor GRABUDP1.0 (in vivo); P2Y6 KO mice; lysosome biogenesis assay; NF-κB cytokine assay; phagocytosis imaging; CalEx viral expression; cognitive testing Neuron High 38614103
2025 P2Y6R functions as an endogenous receptor for long-chain ceramides (C16:0 ceramide), sensing circulating ceramides to activate Gq/NLRP3 inflammasome signaling in endothelial cells and macrophages, thereby aggravating atherosclerosis; P2Y6R deficiency mitigates ceramide-induced and chronic-kidney-disease-aggravated atherosclerosis without affecting cholesterol/ceramide levels. Systematic GPCR screen (G-protein-signaling quantification + NLRP3 inflammasome assay); P2Y6R and CYSLTR2 genetic/pharmacological inhibition in atherosclerosis mouse models; structural analysis of ceramide-CYSLTR2-Gq complexes (for CYSLTR2); functional validation in endothelial cells and macrophages Nature Medium 40049228

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 661 17410128
1996 Cloning, functional expression and tissue distribution of the human P2Y6 receptor. Biochemical and biophysical research communications 214 8670200
2008 P2Y6 receptor-Galpha12/13 signalling in cardiomyocytes triggers pressure overload-induced cardiac fibrosis. The EMBO journal 161 19008857
2004 Diisothiocyanate derivatives as potent, insurmountable antagonists of P2Y6 nucleotide receptors. Biochemical pharmacology 138 15081875
2008 Knockout mice reveal a role for P2Y6 receptor in macrophages, endothelial cells, and vascular smooth muscle cells. Molecular pharmacology 128 18523137
2014 Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo. Glia 123 24838858
2008 Intestinal inflammation increases the expression of the P2Y6 receptor on epithelial cells and the release of CXC chemokine ligand 8 by UDP. Journal of immunology (Baltimore, Md. : 1950) 107 18250478
2010 Selective induction of endothelial P2Y6 nucleotide receptor promotes vascular inflammation. Blood 103 21173118
2005 Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway. Blood 97 16322472
2002 P2X(1) receptor-deficient mice establish the native P2X receptor and a P2Y6-like receptor in arteries. Molecular pharmacology 96 12435812
2005 P2Y6 nucleotide receptors activate NF-kappaB and increase survival of osteoclasts. The Journal of biological chemistry 94 15722352
2011 Uridine 5'-diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor. Journal of immunology (Baltimore, Md. : 1950) 88 21317391
2000 P2Y(1), P2Y(2), P2Y(4), and P2Y(6) receptors are coupled to Rho and Rho kinase activation in vascular myocytes. American journal of physiology. Heart and circulatory physiology 88 10843869
2006 Synthesis and structure-activity relationships of uracil nucleotide derivatives and analogues as agonists at human P2Y2, P2Y4, and P2Y6 receptors. Journal of medicinal chemistry 85 17125260
1997 Slow desensitization of the human P2Y6 receptor. European journal of pharmacology 85 9226417
2006 Positive inotropic effects by uridine triphosphate (UTP) and uridine diphosphate (UDP) via P2Y2 and P2Y6 receptors on cardiomyocytes and release of UTP in man during myocardial infarction. Circulation research 83 16543499
2011 P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. Journal of immunology (Baltimore, Md. : 1950) 76 22102722
2002 Methanocarba modification of uracil and adenine nucleotides: high potency of Northern ring conformation at P2Y1, P2Y2, P2Y4, and P2Y11 but not P2Y6 receptors. Journal of medicinal chemistry 76 11754592
2020 P2Y6 receptor inhibition aggravates ischemic brain injury by reducing microglial phagocytosis. CNS neuroscience & therapeutics 74 32154670
2015 Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell 73 26359991
2016 Purinergic P2Y6 receptors heterodimerize with angiotensin AT1 receptors to promote angiotensin II-induced hypertension. Science signaling 69 26787451
2016 P2Y6 Receptor Antagonist MRS2578 Inhibits Neutrophil Activation and Aggregated Neutrophil Extracellular Trap Formation Induced by Gout-Associated Monosodium Urate Crystals. Journal of immunology (Baltimore, Md. : 1950) 69 27903742
2003 P2Y6 receptor mediates colonic NaCl secretion via differential activation of cAMP-mediated transport. The Journal of clinical investigation 69 12569163
2002 UDP acts as a growth factor for vascular smooth muscle cells by activation of P2Y(6) receptors. American journal of physiology. Heart and circulatory physiology 66 11788430
2024 Microglial P2Y6 calcium signaling promotes phagocytosis and shapes neuroimmune responses in epileptogenesis. Neuron 65 38614103
2016 Central Role of P2Y6 UDP Receptor in Arteriolar Myogenic Tone. Arteriosclerosis, thrombosis, and vascular biology 64 27255725
2021 The microglial P2Y6 receptor mediates neuronal loss and memory deficits in neurodegeneration. Cell reports 63 34965424
2013 ATP released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors. Biochemical pharmacology 62 24269631
2014 Role of spinal P2Y6 and P2Y11 receptors in neuropathic pain in rats: possible involvement of glial cells. Molecular pain 61 24886406
2014 P2Y6 deficiency limits vascular inflammation and atherosclerosis in mice. Arteriosclerosis, thrombosis, and vascular biology 61 25104800
1998 Expression of the P2Y6 purinergic receptor in human T cells infiltrating inflammatory bowel disease. Laboratory investigation; a journal of technical methods and pathology 61 9840612
2004 Expression of P2Y1, P2Y2, P2Y4, and P2Y6 receptor subtypes in the rat retina. Investigative ophthalmology & visual science 60 15452043
2014 Extracellular UDP and P2Y6 function as a danger signal to protect mice from vesicular stomatitis virus infection through an increase in IFN-β production. Journal of immunology (Baltimore, Md. : 1950) 58 25261483
2006 Structure-activity relationships of uridine 5'-diphosphate analogues at the human P2Y6 receptor. Journal of medicinal chemistry 58 16942026
2014 P2Y6 receptor potentiates pro-inflammatory responses in macrophages and exhibits differential roles in atherosclerotic lesion development. PloS one 57 25360548
2008 Synthesis and potency of novel uracil nucleotides and derivatives as P2Y2 and P2Y6 receptor agonists. Bioorganic & medicinal chemistry 56 18514530
2020 Microglia Purinoceptor P2Y6: An Emerging Therapeutic Target in CNS Diseases. Cells 54 32630251
2017 Microglia P2Y6 receptor is related to Parkinson's disease through neuroinflammatory process. Journal of neuroinflammation 54 28219441
2018 The G protein-coupled P2Y₆ receptor promotes colorectal cancer tumorigenesis by inhibiting apoptosis. Biochimica et biophysica acta. Molecular basis of disease 53 29454075
2014 Microglia P2Y₆ receptors mediate nitric oxide release and astrocyte apoptosis. Journal of neuroinflammation 53 25178395
2003 P2Y6 nucleotide receptor activates PKC to protect 1321N1 astrocytoma cells against tumor necrosis factor-induced apoptosis. Cellular and molecular neurobiology 49 12825835
2000 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. The Journal of biological chemistry 49 11114308
2025 Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis. Nature 48 40049228
2019 P2Y6 and P2X7 Receptor Antagonism Exerts Neuroprotective/ Neuroregenerative Effects in an Animal Model of Parkinson's Disease. Frontiers in cellular neuroscience 48 31787881
2015 P2Y6 Receptor-Mediated Microglial Phagocytosis in Radiation-Induced Brain Injury. Molecular neurobiology 48 26099306
2013 The P2Y6 receptor mediates Clostridium difficile toxin-induced CXCL8/IL-8 production and intestinal epithelial barrier dysfunction. PloS one 48 24278446
2011 P2Y6 receptor contributes to neutrophil recruitment to inflamed intestinal mucosa by increasing CXC chemokine ligand 8 expression in an AP-1-dependent manner in epithelial cells. Inflammatory bowel diseases 48 22095787
1999 Dual coupling of heterologously-expressed rat P2Y6 nucleotide receptors to N-type Ca2+ and M-type K+ currents in rat sympathetic neurones. British journal of pharmacology 48 10193782
2013 The activation of P2Y6 receptor in cultured spinal microglia induces the production of CCL2 through the MAP kinases-NF-κB pathway. Neuropharmacology 45 23916475
2005 The pyrimidinergic P2Y6 receptor mediates a novel release of proinflammatory cytokines and chemokines in monocytic cells stimulated with UDP. Biochemical and biophysical research communications 45 15796906
2024 Macrophage P2Y6 receptor deletion attenuates atherosclerosis by limiting foam cell formation through phospholipase Cβ/store-operated calcium entry/calreticulin/scavenger receptor A pathways. European heart journal 43 38036416
2017 Inhibition of P2Y6 Signaling in AgRP Neurons Reduces Food Intake and Improves Systemic Insulin Sensitivity in Obesity. Cell reports 42 28199831
2014 Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats. Pharmacology, biochemistry, and behavior 41 25449358
2011 Structural modifications of UMP, UDP, and UTP leading to subtype-selective agonists for P2Y2, P2Y4, and P2Y6 receptors. Journal of medicinal chemistry 41 21417463
2011 The P2Y(6) receptor stimulates bone resorption by osteoclasts. Endocrinology 41 21828185
2007 Comparative analysis of P2Y4 and P2Y6 receptor architecture in native and transfected neuronal systems. Biochimica et biophysica acta 41 17481575
2004 Evidence for P2Y1, P2Y2, P2Y6 and atypical UTP-sensitive receptors coupled to rises in intracellular calcium in mouse cultured superior cervical ganglion neurons and glia. British journal of pharmacology 41 15466449
2014 Enhancement of glucose uptake in mouse skeletal muscle cells and adipocytes by P2Y6 receptor agonists. PloS one 40 25549240
2005 Purinergic P2Y6 receptors induce Ca2+ and CFTR dependent Cl- secretion in mouse trachea. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 40 16121038
2020 Lack of adipocyte purinergic P2Y6 receptor greatly improves whole body glucose homeostasis. Proceedings of the National Academy of Sciences of the United States of America 39 33199639
2016 Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation. Oncotarget 39 27074554
2012 Autocrine regulation of γ-irradiation-induced DNA damage response via extracellular nucleotides-mediated activation of P2Y6 and P2Y12 receptors. DNA repair 38 22682873
2021 NTPDase8 protects mice from intestinal inflammation by limiting P2Y6 receptor activation: identification of a new pathway of inflammation for the potential treatment of IBD. Gut 37 33452178
2019 Exacerbated intestinal inflammation in P2Y6 deficient mice is associated with Th17 activation. Biochimica et biophysica acta. Molecular basis of disease 37 31271845
2017 Anti-proliferative Effects of Nucleotides on Gastric Cancer via a Novel P2Y6/SOCE/Ca2+/β-catenin Pathway. Scientific reports 37 28550303
2001 Evidence for basolateral P2Y(6) receptors along the rat proximal tubule: functional and molecular characterization. Journal of the American Society of Nephrology : JASN 37 11461936
1998 Evidence that the p2y3 receptor is the avian homologue of the mammalian P2Y6 receptor. Molecular pharmacology 37 9730913
2017 P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis. Frontiers in immunology 35 28878780
2008 Uridine diphosphate (UDP) stimulates insulin secretion by activation of P2Y6 receptors. Biochemical and biophysical research communications 35 18387359
2013 Lack of specificity shown by P2Y6 receptor antibodies. Naunyn-Schmiedeberg's archives of pharmacology 34 23793102
2014 P2Y6 receptor-mediated proinflammatory signaling in human bronchial epithelia. PloS one 33 25243587
2013 Inhibition of P2X4 function by P2Y6 UDP receptors in microglia. Glia 33 24123515
1997 Cloning of P2Y6 cDNAs and identification of a pseudogene: comparison of P2Y receptor subtype expression in bone and brain tissues. Biochemical and biophysical research communications 33 9412455
2017 Prostaglandin E2 glyceryl ester is an endogenous agonist of the nucleotide receptor P2Y6. Scientific reports 32 28539604
2010 Pyrimidine ribonucleotides with enhanced selectivity as P2Y(6) receptor agonists: novel 4-alkyloxyimino, (S)-methanocarba, and 5'-triphosphate gamma-ester modifications. Journal of medicinal chemistry 32 20446735
2005 Purinergic receptors in human placenta: evidence for functionally active P2X4, P2X7, P2Y2, and P2Y6. American journal of physiology. Regulatory, integrative and comparative physiology 32 16373435
2022 P2Y6 receptor-dependent microglial phagocytosis of synapses mediates synaptic and memory loss in aging. Aging cell 31 36565471
2008 Apical versus basolateral P2Y(6) receptor-mediated Cl(-) secretion in immortalized bronchial epithelia. American journal of respiratory cell and molecular biology 31 19011163
2012 Identification of contractile P2Y1, P2Y6, and P2Y12 receptors in rat intrapulmonary artery using selective ligands. The Journal of pharmacology and experimental therapeutics 30 22991416
2010 Involvement of P2Y6 receptor in p38 MAPK-mediated COX-2 expression in response to UVB irradiation of human keratinocytes. Radiation research 30 21388279
2005 Distribution of P2Y6 and P2Y12 receptor: their colocalization with calbindin, calretinin and nitric oxide synthase in the guinea pig enteric nervous system. Histochemistry and cell biology 30 16195889
2009 P2Y6 receptors require an intact cysteinyl leukotriene synthetic and signaling system to induce survival and activation of mast cells. Journal of immunology (Baltimore, Md. : 1950) 29 19124756
2003 Potent P2Y6 receptor mediated contractions in human cerebral arteries. BMC pharmacology 29 12737633
2015 Activation of P2Y6 Receptors Facilitates Nonneuronal Adenosine Triphosphate and Acetylcholine Release from Urothelium with the Lamina Propria of Men with Bladder Outlet Obstruction. The Journal of urology 28 26004864
2014 Purine receptor P2Y6 mediates cellular response to γ-ray-induced DNA damage. The Journal of toxicological sciences 28 24418705
2008 Attenuation of apoptosis in vitro and ischemia/reperfusion injury in vivo in mouse skeletal muscle by P2Y6 receptor activation. Pharmacological research 28 18805489
2022 Redox-dependent internalization of the purinergic P2Y6 receptor limits colitis progression. Science signaling 27 35015570
2016 New insights on pyrimidine signalling within the arterial vasculature - Different roles for P2Y2 and P2Y6 receptors in large and small coronary arteries of the mouse. Journal of molecular and cellular cardiology 27 26827897
2009 Blockade of murine T cell activation by antagonists of P2Y6 and P2X7 receptors. Biochemical and biophysical research communications 27 19426712
2007 UDP facilitates microglial phagocytosis through P2Y6 receptors. Cell adhesion & migration 27 19262132
2019 P2Y6 signaling in alveolar macrophages prevents leukotriene-dependent type 2 allergic lung inflammation. The Journal of clinical investigation 26 31638598
2017 Identification of novel selective P2Y6 receptor antagonists by high-throughput screening assay. Life sciences 26 28527783
2014 P2Y₆ receptor inhibition perturbs CCL2-evoked signalling in human monocytic and peripheral blood mononuclear cells. Journal of cell science 26 25271060
2013 Extracellular UDP enhances P2X-mediated bladder smooth muscle contractility via P2Y(6) activation of the phospholipase C/inositol trisphosphate pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 23362118
2014 Activation of P2Y6 receptors increases the voiding frequency in anaesthetized rats by releasing ATP from the bladder urothelium. British journal of pharmacology 25 24697602
2012 UDP made a highly promising stable, potent, and selective P2Y6-receptor agonist upon introduction of a boranophosphate moiety. Bioorganic & medicinal chemistry 25 22901672
2009 P2Y6 receptor and immunoinflammation. Neuroscience bulletin 25 19448690
2017 Purinergic P2Y6 receptors: A new therapeutic target of age-dependent hypertension. Pharmacological research 23 28336370
2016 Loss of Mouse P2Y6 Nucleotide Receptor Is Associated with Physiological Macrocardia and Amplified Pathological Cardiac Hypertrophy. The Journal of biological chemistry 23 27231349
2010 P2Y6 receptors and ADAM17 mediate low-dose gamma-ray-induced focus formation (activation) of EGF receptor. Radiation research 23 21268712

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