Affinage

GPR55

G-protein coupled receptor 55 · UniProt Q9Y2T6

Length
319 aa
Mass
36.6 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: UniProt preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GPR55 is a class A G-protein-coupled receptor that transduces lysophospholipid and cannabinoid signals into Rho-family GTPase and Ca2+ signaling to regulate cell migration, synaptic transmission, metabolism, and tumor growth (PMID:17765871, PMID:17876302, PMID:18757503). Its principal endogenous ligand is L-α-lysophosphatidylinositol (LPI), which drives ERK phosphorylation, GTPγS binding, and Ca2+ transients selectively in GPR55-expressing cells (PMID:17765871), while the receptor is also engaged by cannabinoids such as CP55940, anandamide, and Δ9-THC (PMID:17876302, PMID:18263732) and by additional lipid agonists (PMID:28698140). GPR55 couples to Gα13 (and Gq/G12 in a context-dependent manner) to activate RhoA, Cdc42, and Rac1 (PMID:17876302, PMID:18263732), producing sustained oscillatory Ca2+ release from IP3R-gated intracellular stores and nuclear translocation of NFAT, with parallel induction of ERK1/2, NF-κB, and CREB (PMID:18263732, PMID:18757503, PMID:20136841); ligand-dependent differences in pathway engagement define biased agonism, and agonist binding triggers β-arrestin recruitment and receptor internalization (PMID:19723626, PMID:20136841). Residue-level mapping places LPI and synthetic agonists at an orthosteric site involving K2.60, E3.29, Y3.32, H170, and F6.55, with a Y3.32/M3.36/F6.48 cluster relaying activation (PMID:28005346). GPR55 forms heteromers with CB1 and CB2 receptors in heterologous cells and native brain tissue, reciprocally reshaping transcription factor and ERK signaling (PMID:23161546, PMID:25048571, PMID:24967683). Physiologically GPR55 governs osteoclast polarization and resorption (PMID:19805329), presynaptic Ca2+-dependent release probability and LTP at hippocampal CA3–CA1 synapses (PMID:23472002, PMID:28653801), colonic motility through myenteric neurons (PMID:23603203), intraepithelial lymphocyte migration and intestinal barrier integrity (PMID:29222090), neural stem cell proliferation and neurogenesis (PMID:29888782), retinal axon growth cone dynamics and projection targeting (PMID:26730399), islet insulin secretion and peripheral insulin sensitivity (PMID:27561953, PMID:30148676, PMID:31923454), and endothelial Ca2+ signaling controlling blood-brain barrier permeability (PMID:20735417, PMID:31279825). In disease, an autocrine LPI/GPR55 loop drives proliferation, migration, and metastasis across prostate, ovarian, colon, breast, and pancreatic cancers via ERK overactivation and downstream effectors including ETV4/PEA3 and HBXIP (PMID:20838378, PMID:20818416, PMID:26436760, PMID:27340777, PMID:29188802, PMID:30061636), and LPI/GPR55 signaling through a ROCK/p38 MAPK axis exacerbates myocardial ischemia/reperfusion injury (PMID:31149342).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2007 High

    Establishing GPR55's ligands and G-protein coupling answered whether this orphan receptor was a functional signaling GPCR and identified its transduction machinery.

    Evidence GTPγS binding and G-protein antibody blocking with cannabinoid and LPI ligands in GPR55-transfected cells; downstream RhoA/Cdc42/Rac1 and ERK/Ca2+ readouts

    PMID:17765871 PMID:17876302

    Open questions at the time
    • Relative physiological importance of cannabinoid vs LPI ligands left unresolved
    • Endogenous tissue source of agonist not defined
  2. 2008 High

    Dissecting the second-messenger cascade established that GPR55 mobilizes Ca2+ from internal stores via Gq/G12-RhoA-PLC-IP3R and modulates ion channels, linking receptor activation to neuronal excitability.

    Evidence Ca2+ imaging and M-current electrophysiology in DRG neurons and HEK293 cells with pharmacological pathway dissection; NFAT reporter and internalization assays in stable HEK293-GPR55 lines

    PMID:18263732 PMID:18757503

    Open questions at the time
    • G-protein selectivity (G13 vs Gq) varied by system and remained context-dependent
    • Native neuronal coupling not yet shown by genetic deletion
  3. 2009 High

    Defining the ligand pharmacology and arrestin behavior clarified which compounds are agonists versus antagonists and revealed β-arrestin-dependent trafficking, and the first knockout phenotype assigned GPR55 a role in bone resorption.

    Evidence β-arrestin-GFP biosensor and PKCβII recruitment assays with a ligand panel; GPR55−/− osteoclast cultures with Rho/ERK assays, resorption, and micro-CT

    PMID:19723626 PMID:19805329

    Open questions at the time
    • Conflicting agonist/antagonist classifications across ligands
    • Mechanism linking GPR55 signaling to osteoclast polarization not fully resolved
  4. 2010 Medium

    Identifying a self-sustaining LPI/GPR55 autocrine loop in cancer cells and endothelial Ca2+/channel coupling showed how the receptor drives proliferation and vascular responses.

    Evidence siRNA knockdown, cPLA2/ABCC1 pathway dissection, Akt/ERK assays in cancer lines; Ca2+ imaging and patch-clamp with knockdown/overexpression in endothelial cells; biased-agonism reporter panel

    PMID:20136841 PMID:20735417 PMID:20818416 PMID:20838378

    Open questions at the time
    • Cancer findings from single labs
    • In vivo contribution of the autocrine loop to tumor growth not yet tested by knockout
  5. 2011 High

    Showing G13/RhoA-dependent cytoskeletal remodeling and immune-cell GTPase crosstalk linked GPR55 to morphological control of migration and polarization.

    Evidence GPR55 siRNA and C3 toxin RhoA inactivation with neurite morphometry in PC12 cells; migration/degranulation/ROS and Rac2/Cdc42 assays in neutrophils

    PMID:21467997 PMID:21904624

    Open questions at the time
    • Endogenous cannabinoid responsiveness was cell-type dependent (absent in PC12)
    • Immune crosstalk mechanism single-lab
  6. 2014 High

    Demonstrating GPR55-CB1 and GPR55-CB2 heteromers established that receptor oligomerization reshapes signaling output, providing a mechanism for context-dependent cannabinoid pharmacology.

    Evidence Co-IP, BRET, proximity ligation in cells and native striatum; NFAT/SRE/NF-κB/CREB and ERK1/2 readouts with label-free assays

    PMID:23161546 PMID:24967683 PMID:25048571

    Open questions at the time
    • Stoichiometry and tissue distribution of heteromers not quantified
    • Functional relevance in vivo only inferred from fingerprint
  7. 2013 High

    Genetic deletion in defined neural circuits assigned GPR55 a presynaptic role controlling release probability and a role in colonic motility, moving beyond heterologous systems.

    Evidence GPR55−/− mice with two-photon presynaptic Ca2+ imaging and optical quantal analysis in hippocampal slices; muscle strip contraction and in vivo transit with O-1602/CBD

    PMID:23472002 PMID:23603203

    Open questions at the time
    • Identity of the presynaptic phospholipid agonist not pinned down
    • Coupling between receptor activation and store Ca2+ release at boutons not molecularly resolved
  8. 2017 High

    Residue-level mutagenesis and structural modeling defined the orthosteric binding pocket and the activation-relaying residue cluster, providing the first structural framework for GPR55 ligand recognition.

    Evidence Site-directed mutagenesis with SRE/SRF reporters on a δ-opioid-based homology model

    PMID:28005346

    Open questions at the time
    • No experimental structure
    • Model-based binding mode for diverse lipid ligands not crystallographically confirmed
  9. 2017 High

    Expanding the in vivo physiology through knockouts placed GPR55 in neurogenesis, retinal axon targeting, intraepithelial lymphocyte behavior, synaptic plasticity, and nociception.

    Evidence GPR55−/− mice with neurogenesis IHC, growth-cone morphometry and retinal projection analysis, intravital IEL imaging, hippocampal LTP electrophysiology, and PAG Ca2+/behavioral nociception assays

    PMID:25972448 PMID:26730399 PMID:28653801 PMID:28698140 PMID:29222090 PMID:29888782

    Open questions at the time
    • Several phenotypes from single labs
    • Downstream effectors in each tissue incompletely mapped
  10. 2018 High

    Knockout and CRISPR studies established GPR55 as a regulator of metabolic homeostasis, controlling insulin secretion from islets and systemic insulin sensitivity.

    Evidence GPR55−/− and CRISPR knockout beta cells/islets with Ca2+ microfluorimetry and insulin secretion; insulin tolerance tests and insulin-signaling Western blots across muscle, fat, and liver

    PMID:27561953 PMID:30148676 PMID:31923454

    Open questions at the time
    • Direct ligand driving islet GPR55 in vivo uncertain
    • Tissue-autonomous vs systemic contributions to insulin resistance not fully separated
  11. 2019 High

    Cancer and cardiac knockout/pathway studies defined disease-relevant effector arms, linking GPR55 to ERK-driven metastatic programs and a ROCK/p38 ischemia/reperfusion axis.

    Evidence Gpr55 ablation in KPC pancreatic cancer mice and xenografts with MAPK/ETV4/HBXIP dissection; isolated GPR55−/− heart I/R model with ROCK/p38 phosphorylation and CBD/Y-27632 pharmacology

    PMID:26436760 PMID:27340777 PMID:29188802 PMID:30061636 PMID:31149342 PMID:31279825

    Open questions at the time
    • Effector pathways (ETV4, HBXIP, ROCK/p38) characterized in individual labs
    • Therapeutic tractability of GPR55 antagonism in these diseases untested clinically

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct ligands, G-protein/arrestin coupling states, and CB receptor heteromerization are integrated to select tissue-specific outputs remains unresolved.
  • No experimental high-resolution structure of activated GPR55 with ligand and transducer
  • Rules governing biased agonism across tissues not defined
  • Endogenous agonist identity in each physiological context often inferred rather than proven

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-1643685 Disease 5 R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1430728 Metabolism 3
Partners
ARRB2CB1CB2GNA13
Complex memberships
GPR55-CB1 heteromerGPR55-CB2 heteromer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 GPR55 binds to and is activated by the cannabinoid ligand CP55940, as well as endocannabinoids anandamide and virodhamine (nM potency), and couples to Gα13, mediating activation of RhoA, Cdc42, and Rac1 downstream. GTPγS binding assay in GPR55-transfected cells; antibody/peptide blocking of G-protein coupling; downstream signaling pathway measurements British journal of pharmacology High 17876302
2007 Lysophosphatidylinositol (LPI) is an endogenous ligand for GPR55: LPI induced rapid ERK phosphorylation, Ca2+ transients, and GTPγS binding specifically in GPR55-expressing HEK293 cells but not in vector-transfected controls. Transient and stable GPR55 expression in HEK293 cells; ERK phosphorylation assay; Ca2+ mobilization assay; GTPγS binding Biochemical and biophysical research communications High 17765871
2008 GPR55 is activated by cannabinoids (Δ9-THC, methanandamide, JWH015) in dorsal root ganglion neurons and HEK293 cells, increasing intracellular calcium via a pathway involving Gq, G12, RhoA, actin, phospholipase C, and IP3R-gated Ca2+ release from stores; GPR55 activation also inhibits M current. Calcium imaging in DRG neurons and HEK293 cells transiently expressing GPR55; pharmacological pathway dissection; electrophysiology (M current recording) Proceedings of the National Academy of Sciences of the United States of America High 18263732
2008 LPI induces GPR55 internalization, stimulates sustained oscillatory Ca2+ release dependent on Gα13 and RhoA activation, and activates NFAT family transcription factors leading to their nuclear translocation in HEK293 cells stably expressing GPR55. Stable GPR55-expressing HEK293 cell line; Ca2+ imaging; receptor internalization assay; NFAT luciferase reporter and nuclear translocation assay; siRNA/dominant-negative approaches FASEB journal High 18757503
2009 GPR55 activation stimulates mouse and human osteoclast polarization and resorption and causes activation of Rho and ERK1/2; these effects were attenuated in osteoclasts generated from GPR55−/− macrophages and by the GPR55 antagonist cannabidiol. GPR55−/− mouse osteoclast cultures; Rho/ERK1/2 activation assays; resorption assays; pharmacological antagonism with cannabidiol; bone histomorphometry and micro-CT of GPR55−/− mice Proceedings of the National Academy of Sciences of the United States of America High 19805329
2009 AM251 and SR141716A (CB1 antagonists) and LPI act as GPR55 agonists driving β-arrestin trafficking and PKCβII activation, while CP55,940 acts as a GPR55 antagonist/partial agonist, blocking GPR55 internalization, β-arrestin–GPR55 complex formation, and ERK1/2 phosphorylation. β-arrestin-GFP biosensor assay; receptor internalization assay; ERK1/2 phosphorylation; PKCβII membrane recruitment in GPR55-transfected cells The Journal of biological chemistry High 19723626
2010 GPR55 promotes cancer cell proliferation and anchorage-independent growth via ERK cascade overactivation in both cell culture and xenografted mice. GPR55 siRNA knockdown and pharmacological blockade in prostate/ovarian cancer cells; ERK1/2 activation assays; xenograft studies Oncogene Medium 20818416 20838378
2010 LPI/GPR55 signaling defines an autocrine loop in cancer cells: LPI is synthesized by cytosolic phospholipase A2, exported by ABCC1/MRP1, and activates GPR55 to stimulate Ca2+ mobilization, Akt, and ERK1/2, driving proliferation. GPR55 siRNA knockdown; pharmacological blockade; Ca2+ mobilization; Akt and ERK1/2 phosphorylation assays in prostate/ovarian cancer lines Oncogene Medium 20838378
2010 LPI elicits GPR55-dependent, GDPβS- and U73122-sensitive, rapid intracellular Ca2+ release coupled to BK(Ca) channel activation and membrane hyperpolarization in endothelial cells; a subsequent GPR55-independent depolarization phase involves non-selective cation channels. siRNA knockdown and overexpression of GPR55 in EA.hy296 endothelial cells; Ca2+ imaging; patch-clamp electrophysiology; membrane potential measurements British journal of pharmacology High 20735417
2011 LPI causes neurite retraction in differentiated PC12 cells expressing endogenous GPR55 through a G13-dependent (not Gq-dependent) and RhoA-dependent pathway; GPR55 siRNA knockdown and RhoA inactivation both prevented this effect. Cannabinoids did not activate endogenous GPR55 in PC12 cells. GPR55 siRNA knockdown; C3 toxin (RhoA inactivation); Ca2+ imaging; RhoA activity assay; neurite morphology measurements in NGF-differentiated PC12 cells PloS one High 21904624
2011 GPR55 activation augments CB2R-mediated neutrophil migration while inhibiting degranulation and ROS production; cross-talk occurs at the level of small GTPases Rac2 and Cdc42, promoting cellular polarization. GPR55 and CB2R agonists in human neutrophils, HEK293, and HL60 cells; migration assays; degranulation and ROS measurements; small GTPase activation assays Cell research Medium 21467997
2012 GPR55 and CB1 receptors form heteromers in HEK293 cells; co-expression of CB1R inhibits GPR55-mediated NFAT and SRE transcription factor activation and ERK1/2 activation, while GPR55 presence enhances CB1R-mediated ERK1/2 and NFAT activation. Co-immunoprecipitation; BRET; NFAT, SRE, ERK1/2 reporter/activation assays in HEK293 cells co-expressing both receptors The Journal of biological chemistry High 23161546
2013 GPR55 activation in hippocampal presynaptic boutons (where it co-localizes with VGLUT1) transiently increases release probability at individual CA3–CA1 synapses via presynaptic Ca2+ release from internal stores; postsynaptic stores are unaffected. The pathway involves phospholipid synthesis in the presynaptic cell but not endocannabinoids 2-AG or AEA. Two-photon Ca2+ imaging in presynaptic axonal boutons; optical quantal analysis at postsynaptic dendritic spines; GPR55 genetic deletion; cannabidiol antagonism; IP3 spot-uncaging; immunolocalization with VGLUT1 in acute hippocampal slices Proceedings of the National Academy of Sciences of the United States of America High 23472002
2013 GPR55 localized to myenteric neurons in mouse and human colon mediates colonic motility; the GPR55 agonist O-1602 reduced evoked contractions (~60%) and slowed colonic transit in WT but not GPR55−/− mice, effects reversed by cannabidiol but not CB1/CB2 antagonists. GPR55−/− mice; muscle strip contraction assays; in vivo GI transit (whole gut and colonic bead expulsion); immunohistochemistry; RT-PCR Neuropharmacology High 23603203
2014 GPR55 and CB2 receptors form heteromers in HEK293 cells and cancer cells (confirmed by co-IP and BRET); heteromerization reduces GPR55-mediated transcription factor activation (NFAT, NF-κB, CREB) but potentiates ERK1/2-MAPK activation, and modifies CB2R signaling. Co-immunoprecipitation; BRET; label-free DMR and CellKey impedance assays; ERK1/2 activation; gene reporter assays in HEK293 cells British journal of pharmacology High 25048571
2014 CB1 and GPR55 receptors form heteromers in rat and monkey striatum (confirmed by BRET and proximity ligation assays); the heteromeric fingerprint (cross-antagonism in ERK1/2 phosphorylation and GPR55-mediated NFAT activation) was detected both in heterologous cells and in native rat brain slices. BRET; in situ proximity ligation assay (PLA) in rat brain slices and non-human primate striatum; ERK1/2 and NFAT assays Experimental neurology High 24967683
2015 GPR55 activation by LPI promotes growth cone enlargement, increased filopodia, and chemo-attractive axon growth in retinal ganglion cells; GPR55−/− neurons have smaller growth cones and reduced outgrowth. In vivo, GPR55 deletion reduces retinal projection branching in dorsal terminal nucleus and eye-specific segregation in superior colliculus and dLGN. GPR55−/− mouse embryo neuron cultures; growth cone morphometry; outgrowth assay; pharmacological LPI, O-1602, and CBD treatments; in vivo retinal projection analysis by immunohistochemistry eNeuro High 26730399
2015 GPR55 activation by LPI in the periaqueductal gray (PAG) increases intracellular Ca2+ via IP3R-dependent ER release and P/Q-type voltage-gated Ca2+ channel entry, depolarizes PAG neurons, and upon intra-PAG injection reduces nociceptive threshold (pronociceptive effect); both effects are abolished by selective GPR55 antagonist ML-193. Ca2+ imaging in dissociated rat PAG neurons; electrophysiology; intra-PAG microinjection; hot-plate nociception test; ML-193 pharmacological antagonism Molecular pharmacology Medium 25972448
2015 GPR55 promotes migration and adhesion of HCT116 colon cancer cells to endothelial cells; LPI increases migration and decreases endothelial monolayer integrity in a GPR55-dependent manner; GPR55 antagonism or siRNA knockdown reduces cancer cell liver metastasis in a mouse model. Adhesion and migration assays; GPR55 siRNA knockdown; pharmacological antagonism (CID16020046, cannabidiol); in vivo mouse liver metastasis model; endothelial integrity assay British journal of pharmacology Medium 26436760
2016 LPI/GPR55 promotes metastasis in triple-negative breast cancer cells by coupling to Gq/11 proteins and activating ERK, which drives the transcription factor ETV4/PEA3 to confer pro-invasive features in vitro and in vivo. GPR55 overexpression/knockdown in breast cancer cells; in vitro invasion assays; in vivo metastasis models; ERK and ETV4/PEA3 signaling pathway analyses; Gq/11 inhibition Oncotarget Medium 27340777
2016 GPR55 mediates Ca2+ mobilization and insulin secretion in mouse and human islets; O-1602-stimulated Ca2+ increase and insulin secretion are abolished in GPR55−/− mouse islets, demonstrating GPR55 dependence for these agonist effects. GPR55−/− mouse islets; Fura-2 Ca2+ microfluorimetry; dynamic insulin secretion (radioimmunoassay); RhoA pull-down; human islet experiments Diabetes, obesity & metabolism High 27561953
2017 Two key residues, K2.60 and E3.29, are crucial for agonist (LPI and ML184) signaling at GPR55, forming the primary ligand interaction site; Y3.32, H170, and F6.55 form the orthosteric binding site; a Y3.32/M3.36/F6.48 cluster is important for the signaling cascade; C10 and C260 form a disulfide bridge occluding TMH1-TMH7 entry. Site-directed mutagenesis; SRE and SRF luciferase reporter assays; GPR55 R* homology model based on δ-opioid receptor crystal structure Biochemistry High 28005346
2017 GPR55 promotes migration and filopodia formation in breast cancer cells via two pathways: HBXIP/p-ERK1/2/Capn4 and MLCK/MLC signaling; GPR55 upregulates HBXIP at the promoter level; GPR55 loss impairs metastatic foci formation in xenograft models. siRNA GPR55 knockdown; CID16020046 antagonism; filopodia assay; migration assays; dual-luciferase HBXIP promoter assay; xenograft nude mouse metastasis model Acta pharmacologica Sinica Medium 29188802
2017 GPR55 activation in neural stem cells significantly increases proliferation (blocked by ML193 antagonist) and promotes neuronal differentiation; in vivo, hippocampal GPR55 activation increases Ki67+, DCX+, and BrdU+ cells, and GPR55−/− mice show reduced hippocampal neurogenesis. Flow cytometry of hNSC proliferation/differentiation; GPR55−/− mouse hippocampal cannula infusion with osmotic pump; immunohistochemistry (Ki67, DCX, BrdU) British journal of pharmacology Medium 29888782
2017 GPR55 activation by LPI elicits intracellular Ca2+ signaling in brain microvascular endothelial cells via voltage-gated Ca2+ channels (not PLC), activates Ca2+-activated K+ channels causing membrane hyperpolarization, transiently disrupts tight and adherens junctions and F-actin, reduces electrical resistance of endothelial monolayers, and increases BBB permeability in vivo. Ca2+ imaging; patch-clamp; ECIS (transendothelial resistance); immunofluorescence of junction proteins; Evans Blue BBB permeability assay in rats; ML-193 antagonism Neuroscience High 31279825
2018 GPR55 deficiency in mice causes increased adiposity, reduced insulin sensitivity in skeletal muscle, adipose, and liver (reduced PKB/Akt phosphorylation and downstream targets), impaired insulin receptor substrate-1 in muscle and increased PTEN in liver/fat; conversely, GPR55 activation enhances insulin signaling in cultured cells in a receptor-dependent manner. GPR55−/− mice; insulin tolerance tests; Western blotting of insulin signaling intermediates; GPR55 agonist/antagonist/siRNA in cultured L6 myotubes, 3T3-L1 adipocytes, hepatocytes FASEB journal High 30148676
2019 LPI exacerbates myocardial ischemia/reperfusion injury in a GPR55- and ROCK-dependent manner: LPI induces ROCK and p38 MAPK phosphorylation in cardiomyocytes (prevented by ROCK inhibitor Y-27632 and CBD), and increases infarct size in isolated WT but not GPR55−/− mouse hearts. Dynamic mass redistribution (DMR) assay in mouse and human iPSC cardiomyocytes; ROCK/p38 MAPK phosphorylation (Western blot); isolated heart I/R model in WT and GPR55−/− mice; infarct size measurement; ROCK inhibitor Y-27632 and CBD pharmacology Pharmacology research & perspectives High 31149342
2018 GPR55 signaling promotes pancreatic cancer cell growth in vitro and in vivo; knockdown or pharmacologic inhibition reduces MAPK signaling, cell cycle progression, and ribonucleotide reductase protein levels; p53 regulates GPR55 protein expression through microRNA miR34b-3p; genetic ablation of Gpr55 in KPC mice significantly prolongs survival. Gpr55 CRISPR/genetic ablation in KPC mouse model; siRNA knockdown; pharmacological GPR55 inhibition (CBD); MAPK signaling Western blots; cell cycle analysis; miR34b-3p functional studies; KPC mouse survival analysis Oncogene High 30061636
2017 GPR55 negatively regulates intraepithelial lymphocyte (IEL) migration speed and epithelial interactions in response to LPI; GPR55−/− IELs migrate faster and interact more extensively with epithelial cells by intravital imaging; GPR55 deficiency or antagonism protects against NSAID-induced intestinal permeability increases. GPR55−/− mice; intravital two-photon imaging of IEL migration; IEL accumulation counts; intestinal permeability assay; short-term GPR55 antagonist treatment Science immunology High 29222090
2017 N-arachidonoyl glycine (NAGly) is an endogenous GPR55 agonist, inducing concentration-dependent Ca2+ mobilization and MAPK activation in GPR55-expressing CHO cells, effects attenuated by the selective GPR55 antagonist ML193. Ca2+ mobilization assay; ERK/MAPK phosphorylation in HAGPR55/CHO cells; ML193 pharmacological antagonism Biochemical and biophysical research communications Medium 28698140
2017 Lysophosphatidylcholine (LPC) activates GPR55 to elicit intracellular Ca2+ mobilization in GPR55-expressing PC-3 cells; this response is blocked by GPR55 antagonists CID16020046 and ML193 and by lipid raft disruption; molecular modeling indicates LPC interacts with overlapping residues as LPI. Ca2+ mobilization assay in PC-3 cells; GPR55 antagonist pharmacology; lipid raft disruption with methyl-β-cyclodextrin; molecular docking modeling Biochemical and biophysical research communications Low 28552522
2020 CRISPR/Cas9-generated Gpr55 knockout beta cells show abolished O-1602-induced Ca2+ release and insulin secretion, and impaired responses to Abn-CBD, AM251, and PEA; GPR55 antagonism in vivo attenuates glucoregulatory effects of Abn-CBD, establishing GPR55 as a mediator of insulinotropic effects. CRISPR/Cas9 Gpr55 knockout in BRIN-BD11 beta cells; Ca2+ mobilization assay; insulin secretion assay; in vivo HFD diabetic mouse studies with GPR55 antagonism Peptides High 31923454
2011 GPR55 ligands promote signaling through multiple downstream pathways including Ca2+, ERK1/2 MAPK, NFAT, NF-κB, and CREB with ligand-dependent differences in potency and efficacy (functional selectivity/biased agonism); receptor endocytosis was also observed. Ca2+ signaling; ERK1/2 phosphorylation; NFAT, NF-κB, CREB reporter assays; receptor endocytosis; dynamic mass redistribution optical assay in stable HEK293-GPR55 cells British journal of pharmacology Medium 20136841
2022 Curcumin activates GPR55 as an agonist; the F190(5.47) residue of GPR55 is important for curcumin interaction; GPR55 activation by curcumin induces SRE/SRF-mediated transcription (blocked by Rho kinase and GPR55 antagonists) and stimulates GLP-1 secretion in GLUTag cells. GPCR expression screening system; SRE/SRF luciferase reporter assays; GPR55 residue mutagenesis (F190A); GLP-1 secretion assay in GLUTag cells; Rho kinase inhibitor and GPR55 antagonist pharmacology NPJ science of food Medium 35031622
2017 LPI application to hippocampal slices of GPR55+/+ mice enhances CA1 long-term potentiation (LTP) and increases paired-pulse ratios; these effects are absent in GPR55−/− mice and blocked by the GPR55 antagonist CID16020046, placing GPR55 as a positive modulator of hippocampal synaptic plasticity. Electrophysiology (LTP induction and paired-pulse ratio) in hippocampal slices of GPR55+/+ and GPR55−/− mice; pharmacological antagonism with CID16020046 Hippocampus High 28653801

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 The orphan receptor GPR55 is a novel cannabinoid receptor. British journal of pharmacology 1246 17876302
2008 GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. Proceedings of the National Academy of Sciences of the United States of America 554 18263732
2007 Identification of GPR55 as a lysophosphatidylinositol receptor. Biochemical and biophysical research communications 377 17765871
1999 Identification and cloning of three novel human G protein-coupled receptor genes GPR52, PsiGPR53 and GPR55: GPR55 is extensively expressed in human brain. Brain research. Molecular brain research 276 9931487
2009 The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proceedings of the National Academy of Sciences of the United States of America 256 19805329
2009 The enigmatic pharmacology of GPR55. Trends in pharmacological sciences 236 19233486
2008 The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 234 18757503
2009 Atypical responsiveness of the orphan receptor GPR55 to cannabinoid ligands. The Journal of biological chemistry 216 19723626
2007 The novel endocannabinoid receptor GPR55 is activated by atypical cannabinoids but does not mediate their vasodilator effects. British journal of pharmacology 189 17704827
2010 The putative cannabinoid receptor GPR55 defines a novel autocrine loop in cancer cell proliferation. Oncogene 184 20838378
2009 Receptors for acylethanolamides-GPR55 and GPR119. Prostaglandins & other lipid mediators 182 19615459
2010 Pharmacological characterization of GPR55, a putative cannabinoid receptor. Pharmacology & therapeutics 178 20298715
2013 Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proceedings of the National Academy of Sciences of the United States of America 172 23472002
2007 GPR55: a new member of the cannabinoid receptor clan? British journal of pharmacology 170 17876300
2010 GPR55 ligands promote receptor coupling to multiple signalling pathways. British journal of pharmacology 169 20136841
2011 GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell research 158 21467997
2010 The orphan G protein-coupled receptor GPR55 promotes cancer cell proliferation via ERK. Oncogene 157 20818416
2011 The L-α-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. Diabetes 143 22179809
2011 Minireview: recent developments in the physiology and pathology of the lysophosphatidylinositol-sensitive receptor GPR55. Molecular endocrinology (Baltimore, Md.) 132 21964594
2011 Modulation of L-α-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. The Journal of biological chemistry 128 22027819
2014 Heteromerization of GPR55 and cannabinoid CB2 receptors modulates signalling. British journal of pharmacology 107 25048571
2009 Differential changes in GPR55 during microglial cell activation. FEBS letters 107 19464294
2014 Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. The Journal of biological chemistry 99 24942731
2013 GPR55, a G-protein coupled receptor for lysophosphatidylinositol, plays a role in motor coordination. PloS one 97 23565223
2017 Advances in the Physiology of GPR55 in the Central Nervous System. Current neuropharmacology 95 27488130
2017 GPR55: A therapeutic target for Parkinson's disease? Neuropharmacology 95 28807673
2015 The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Frontiers in pharmacology 92 25926795
2016 GPR55 - a putative "type 3" cannabinoid receptor in inflammation. Journal of basic and clinical physiology and pharmacology 89 26669245
2018 GPR55 signalling promotes proliferation of pancreatic cancer cells and tumour growth in mice, and its inhibition increases effects of gemcitabine. Oncogene 85 30061636
2015 GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. British journal of pharmacology 84 26436760
2018 Lysophosphatidylinositols, from Cell Membrane Constituents to GPR55 Ligands. Trends in pharmacological sciences 82 29588059
2012 The cannabinoid receptor CB1 modulates the signaling properties of the lysophosphatidylinositol receptor GPR55. The Journal of biological chemistry 81 23161546
2015 The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterology and motility 80 26227635
2012 The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas. Oncogene 80 22751111
2011 A novel CB receptor GPR55 and its ligands are involved in regulation of gut movement in rodents. Neurogastroenterology and motility 77 21726355
2014 CB1 and GPR55 receptors are co-expressed and form heteromers in rat and monkey striatum. Experimental neurology 76 24967683
2012 The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 76 22454039
2013 The actions and metabolism of lysophosphatidylinositol, an endogenous agonist for GPR55. Prostaglandins & other lipid mediators 73 23714700
2019 Some Prospective Alternatives for Treating Pain: The Endocannabinoid System and Its Putative Receptors GPR18 and GPR55. Frontiers in pharmacology 67 30670965
2018 Localization of cannabinoid receptors CB1, CB2, GPR55, and PPARα in the canine gastrointestinal tract. Histochemistry and cell biology 64 29882158
2017 GPR55 regulates intraepithelial lymphocyte migration dynamics and susceptibility to intestinal damage. Science immunology 63 29222090
2013 A role for O-1602 and G protein-coupled receptor GPR55 in the control of colonic motility in mice. Neuropharmacology 61 23603203
2010 GPR55: Current knowledge and future perspectives of a purported "Type-3" cannabinoid receptor. Current medicinal chemistry 61 20166924
2011 Pharmacology of GPR55 in yeast and identification of GSK494581A as a mixed-activity glycine transporter subtype 1 inhibitor and GPR55 agonist. The Journal of pharmacology and experimental therapeutics 56 21233197
2015 Role of the lysophosphatidylinositol/GPR55 axis in cancer. Advances in biological regulation 54 26588872
2010 GPR55-dependent and -independent ion signalling in response to lysophosphatidylinositol in endothelial cells. British journal of pharmacology 54 20735417
2012 A potential role for GPR55 in gastrointestinal functions. Current opinion in pharmacology 53 23063456
2011 Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in PC12 cells. PloS one 53 21904624
2018 GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 30148676
2017 GPR55: a new promising target for metabolism? Journal of molecular endocrinology 51 28196832
2017 A putative lysophosphatidylinositol receptor GPR55 modulates hippocampal synaptic plasticity. Hippocampus 51 28653801
2022 The neuroprotective effects of GPR55 against hippocampal neuroinflammation and impaired adult neurogenesis in CSDS mice. Neurobiology of disease 49 35490927
2016 GPR55-dependent stimulation of insulin secretion from isolated mouse and human islets of Langerhans. Diabetes, obesity & metabolism 49 27561953
2015 Central administration of GPR55 receptor agonist and antagonist modulates anxiety-related behaviors in rats. Fundamental & clinical pharmacology 48 25620584
2015 The Lysophosphatidylinositol Receptor GPR55 Modulates Pain Perception in the Periaqueductal Gray. Molecular pharmacology 48 25972448
2017 G protein-coupled receptor GPR55 promotes colorectal cancer and has opposing effects to cannabinoid receptor 1. International journal of cancer 47 28875496
2012 Off-target cannabinoid effects mediated by GPR55. Pharmacology 47 22433274
2014 GPR55: from orphan to metabolic regulator? Pharmacology & therapeutics 45 24972076
2013 Antagonists for the orphan G-protein-coupled receptor GPR55 based on a coumarin scaffold. Journal of medicinal chemistry 45 23679955
2012 GPR55 and GPR35 and their relationship to cannabinoid and lysophospholipid receptors. Life sciences 45 22820167
2015 Role of GPR55 during Axon Growth and Target Innervation. eNeuro 44 26730399
2021 GPR119 and GPR55 as Receptors for Fatty Acid Ethanolamides, Oleoylethanolamide and Palmitoylethanolamide. International journal of molecular sciences 43 33494185
2010 GPR55, a lysophosphatidylinositol receptor with cannabinoid sensitivity? Current topics in medicinal chemistry 40 20370712
2016 Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. Oncotarget 38 27340777
2013 GPR55 and its interaction with membrane lipids: comparison with other endocannabinoid-binding receptors. Current medicinal chemistry 37 23151004
2013 A potential role for GPR55 in the regulation of energy homeostasis. Drug discovery today 37 24370891
2016 Advances Towards The Discovery of GPR55 Ligands. Current medicinal chemistry 36 27109575
2018 Activation of GPR55 increases neural stem cell proliferation and promotes early adult hippocampal neurogenesis. British journal of pharmacology 35 29888782
2010 The putative cannabinoid receptor GPR55 promotes cancer cell proliferation. Oncogene 35 21057532
2021 Activation of GPR55 attenuates cognitive impairment and neurotoxicity in a mouse model of Alzheimer's disease induced by Aβ1-42 through inhibiting RhoA/ROCK2 pathway. Progress in neuro-psychopharmacology & biological psychiatry 34 34363866
2011 Functional polymorphism in the GPR55 gene is associated with anorexia nervosa. Synapse (New York, N.Y.) 34 20506567
2018 Anandamide inhibits FcεRI-dependent degranulation and cytokine synthesis in mast cells through CB2 and GPR55 receptor activation. Possible involvement of CB2-GPR55 heteromers. International immunopharmacology 33 30243065
2017 Inflammatory and Neuropathic Nociception is Preserved in GPR55 Knockout Mice. Scientific reports 32 28428628
2017 The LPI/GPR55 axis enhances human breast cancer cell migration via HBXIP and p-MLC signaling. Acta pharmacologica Sinica 32 29188802
2022 The Cytotoxic Effects of Cannabidiol and Cannabigerol on Glioblastoma Stem Cells May Mostly Involve GPR55 and TRPV1 Signalling. Cancers 30 36497400
2019 Targeting CB1 and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson's Disease. Molecular neurobiology 30 30687889
2007 GPR55 and the vascular receptors for cannabinoids. British journal of pharmacology 30 17704825
2019 Potential metabolic and behavioural roles of the putative endocannabinoid receptors GPR18, GPR55 and GPR119 in feeding. Current neuropharmacology 29 31146657
2017 Lysophosphatidylcholine elicits intracellular calcium signaling in a GPR55-dependent manner. Biochemical and biophysical research communications 29 28552522
2013 Rod photoreceptors express GPR55 in the adult vervet monkey retina. PloS one 28 24244730
2009 Is GPR55 an anandamide receptor? Vitamins and hormones 27 19647110
2022 Identification of G protein-coupled receptor 55 (GPR55) as a target of curcumin. NPJ science of food 26 35031622
2021 GPR55 in the brain and chronic neuropathic pain. Behavioural brain research 25 33745983
2020 Expression of GPR55 and either cannabinoid CB1 or CB2 heteroreceptor complexes in the caudate, putamen, and accumbens nuclei of control, parkinsonian, and dyskinetic non-human primates. Brain structure & function 25 32691218
2019 l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway. Pharmacology research & perspectives 25 31149342
2022 The oncogenic lysophosphatidylinositol (LPI)/GPR55 signaling. Life sciences 24 35500681
2019 GPR55-mediated effects on brain microvascular endothelial cells and the blood-brain barrier. Neuroscience 24 31279825
2017 N-arachidonoyl glycine, another endogenous agonist of GPR55. Biochemical and biophysical research communications 24 28698140
2017 Identification of Crucial Amino Acid Residues Involved in Agonist Signaling at the GPR55 Receptor. Biochemistry 23 28005346
2015 A role for GPR55 in human placental venous endothelial cells. Histochemistry and cell biology 23 25869640
2024 Modulation of neuroinflammation and oxidative stress by targeting GPR55 - new approaches in the treatment of psychiatric disorders. Molecular psychiatry 22 38796643
2016 Selective GPR55 antagonism reduces chemoresistance in cancer cells. Pharmacological research 22 27423937
2014 GPR55 deletion in mice leads to age-related ventricular dysfunction and impaired adrenoceptor-mediated inotropic responses. PloS one 22 25275556
2013 (R,R')-4'-methoxy-1-naphthylfenoterol targets GPR55-mediated ligand internalization and impairs cancer cell motility. Biochemical pharmacology 22 24355564
2020 The cannabinoid ligands SR141716A and AM251 enhance human and mouse islet function via GPR55-independent signalling. Cellular and molecular life sciences : CMLS 19 31925452
2018 Possible role of hippocampal GPR55 in spatial learning and memory in rats. Acta neurobiologiae experimentalis 19 29694340
2020 Antinociceptive Effects of the GPR55 Antagonist CID16020046 Injected into the Rat Anterior Cingulate Cortex. Neuroscience 18 32673629
2017 GPR55 receptor antagonist decreases glycolytic activity in PANC-1 pancreatic cancer cell line and tumor xenografts. International journal of cancer 18 28741686
2020 CRISPR/Cas9 gene editing demonstrates metabolic importance of GPR55 in the modulation of GIP release and pancreatic beta cell function. Peptides 17 31923454
2017 Peptide-guided targeting of GPR55 for anti-cancer therapy. Oncotarget 17 28029647

Missed literature

Know a paper Affinage missed for GPR55? Flag it for the maintainers and the community.

No submissions yet.