Affinage

GRPR

Gastrin-releasing peptide receptor · UniProt P30550

Length
384 aa
Mass
43.2 kDa
Annotated
2026-04-28
100 papers in source corpus 21 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRPR is a G protein-coupled receptor for gastrin-releasing peptide (GRP) that functions as a central integrator of itch signaling in spinal cord circuits, a mediator of neutrophil chemotaxis, and a driver of cancer cell proliferation and organ inflammation. Ligand binding activates PLC/IP3, PI3Kγ/Akt, ERK/MAPK, and NF-κB signaling cascades, and high-affinity GRP recognition depends on extracellular/transmembrane residues K101, Q121, A198, P199, S293, R288, and T297 (PMID:15670577, PMID:26658875, PMID:22203955). In the spinal dorsal horn, GRPR marks glutamatergic vertical interneurons in laminae I–II that receive nociceptive primary afferent input and are gated by local GABAergic (galanin+, nNOS+) and descending inhibitory neurons; GRPR heterodimerizes with MOR1D to mediate opioid-induced itch and with 5-HT1A to potentiate serotonergic itch facilitation (PMID:22000021, PMID:25453842, PMID:35543635, PMID:31676846, PMID:31806757). Beyond itch, GRPR-TLR4 interaction activates STAT1 to drive necroptosis and inflammation in kidney injury, GRPR promotes epithelial-to-mesenchymal transition via TWIST/SNAIL/SLUG upregulation in prostate cancer, and GRPR signals through IRF1/Caspase-1 and NOX2 pathways to exacerbate alcohol-associated liver injury (PMID:37409771, PMID:37415332, PMID:26939805, PMID:38084678).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 Medium

    Establishing the chromosomal locus of GRPR at Xp22.1-p22.2 provided the foundation for genetic studies of this receptor in humans.

    Evidence YAC contig construction and STS mapping on human X chromosome

    PMID:7759104

    Open questions at the time
    • No functional consequence of X-linkage explored
    • No disease-associated variants identified at this locus
  2. 2000 Medium

    Germline Grpr knockout revealed a behavioral role in social interaction and olfactory processing, demonstrating CNS functions beyond gut/cancer biology.

    Evidence Grpr KO mice tested in social interaction and olfactory preference paradigms

    PMID:10869497

    Open questions at the time
    • Circuit basis for social behavior phenotype unknown
    • Not replicated independently
    • Contribution of compensatory NMBR signaling not assessed
  3. 2004 High

    Identification of key ligand-binding residues (K101, Q121, A198, P199, S293, R288, T297) defined the structural determinants of GRP selectivity over related bombesin receptors.

    Evidence Site-directed mutagenesis with radioligand binding and reverse mutations in BRS-3

    PMID:15670577

    Open questions at the time
    • No crystal or cryo-EM structure available
    • Mechanism by which individual residues contribute to selectivity not resolved at atomic level
  4. 2005 Medium

    Demonstration that brain GRPR signals through PLC/diacylglycerol lipase (not PLA2) to drive sympatho-adrenomedullary catecholamine release established tissue-specific signaling pathway utilization.

    Evidence Intracerebroventricular GRP injection with PLC and diacylglycerol lipase inhibitors, plasma catecholamine measurement

    PMID:15910801

    Open questions at the time
    • Single lab pharmacological study
    • Cell type mediating central catecholamine response not identified
  5. 2011 High

    Discovery that MOR1D heterodimerizes with GRPR and that morphine triggers co-internalization with unidirectional cross-activation through PLCβ3/IP3R3 established the molecular mechanism of opioid-induced itch.

    Evidence Co-immunoprecipitation, internalization assays, PLCβ3/IP3R3 KO mice, behavioral assays

    PMID:22000021

    Open questions at the time
    • Structural basis of MOR1D-GRPR heterodimer unknown
    • Relevance to human opioid-induced pruritus not directly tested
  6. 2011 High

    GRPR was shown to mediate GRP-induced neutrophil chemotaxis via PLC-β2, PI3K, ERK, and p38 in a Gαi-independent manner, extending GRPR function to innate immune cell recruitment.

    Evidence In vitro chemotaxis with pharmacological inhibitors and in vivo peritoneal neutrophil recruitment blocked by GRPR antagonist RC-3095

    PMID:22203955

    Open questions at the time
    • Direct G protein coupling in neutrophils not characterized
    • Role in human neutrophil chemotaxis not confirmed
  7. 2013 High

    Electrophysiological dissection in paraventricular thalamic neurons revealed that GRPR activation suppresses an inward rectifier K+ conductance and activates a TRPV1-like non-selective cation conductance, defining the ionic basis of GRP-mediated excitation.

    Evidence Perforated patch clamp in acute brain slices with TRPV1 and BB2 antagonists

    PMID:23359674

    Open questions at the time
    • Whether the same ionic mechanisms operate in spinal GRPR+ neurons is untested
    • Identity of the TRPV1-like channel not molecularly confirmed
  8. 2014 High

    Three studies collectively defined the circuit logic of spinal itch: 5-HT1A-GRPR heteromers potentiate itch signaling, GRPR and NMBR cross-compensate for histaminergic itch, and BNP-NPRA signaling operates independently of the GRP-GRPR pathway.

    Evidence FRET/calcium imaging for 5-HT1A-GRPR interaction; double KO mice for GRPR-NMBR epistasis; pharmacological/genetic blockade for BNP independence

    PMID:24438367 PMID:25209280 PMID:25453842

    Open questions at the time
    • Whether 5-HT1A-GRPR heteromerization occurs in human spinal cord is unknown
    • How GRPR and NMBR cross-inhibit each other biochemically is unresolved
  9. 2015 High

    Identification of PI3Kγ/Akt as a GRPR effector pathway in spinal neurons and DRG neurons expanded the signaling repertoire beyond PLC, showing that GRP directly depolarizes small DRG neurons and induces Akt phosphorylation.

    Evidence Patch clamp, calcium imaging, Akt phosphorylation in ex vivo spinal cord and GRPR-transfected HEK293 cells, PI3Kγ inhibitor reduces scratching

    PMID:26658875

    Open questions at the time
    • Whether PI3Kγ acts in parallel or downstream of PLCβ not resolved
    • DRG GRPR role in itch versus pain not fully dissected
  10. 2016 Medium

    GRPR activation was shown to drive epithelial-to-mesenchymal transition in prostate cancer cells by upregulating TWIST, SNAIL, and SLUG while downregulating E-cadherin, linking receptor signaling to cancer invasion.

    Evidence Stable GRPR transfection in Ace-1 cells, qRT-PCR for EMT markers, in vivo xenograft tumor growth

    PMID:26939805

    Open questions at the time
    • Downstream signaling pathway mediating EMT not identified
    • Relevance to clinical prostate cancer progression not validated
  11. 2019 High

    Circuit mapping established that spinal GRPR+ neurons receive C/Aδ fiber input, contact NK1R+ projection neurons, and are gated by local galanin+ GABAergic, nNOS+ inhibitory, and descending RVM inhibitory neurons, defining the inhibitory control architecture of itch transmission.

    Evidence Electrophysiology, viral tracing, immunohistochemistry, GABAergic pharmacology in spinal cord

    PMID:31676846 PMID:31806757

    Open questions at the time
    • Identity of descending RVM cell types projecting to GRPR+ neurons not fully resolved
    • Whether GRPR+ neuron gating differs in chronic itch states is unknown
  12. 2022 High

    Genetic cell-type identification confirmed GRPR+ neurons as glutamatergic vertical cells in laminae I–outer II that respond to both noxious and pruritic stimuli and whose chemogenetic activation evokes pain and itch behaviors, resolving their modality tuning.

    Evidence GRPR-CreERT2 mice, viral tracing, electrophysiology, DREADD chemogenetics, behavioral assays

    PMID:35543635

    Open questions at the time
    • How GRPR+ neurons differentially encode itch versus pain at the population level is unresolved
    • Contribution of non-GRP ligands to GRPR+ neuron activation in vivo unknown
  13. 2023 High

    GRPR was linked to organ inflammation and injury through three distinct mechanisms: GRPR-TLR4/STAT1-mediated necroptosis in kidney tubular cells, IRF1/Caspase-1 and NOX2-dependent pathways in alcohol-associated liver injury, and NF-κB-driven renal fibrosis in hyperuricemia, with STAT1 establishing a positive feedback loop by inducing GRP synthesis.

    Evidence Global and conditional Grpr KO mice, Co-IP for GRPR-TLR4, ChIP for STAT1, GRPR overexpression rescue, pharmacological antagonist RH-1402, RNA-seq

    PMID:37409771 PMID:37415332 PMID:38084678

    Open questions at the time
    • Whether GRPR-TLR4 interaction is direct or scaffolded not resolved
    • Human relevance of renal and hepatic GRPR pathology requires clinical validation
    • Specificity of STAT1 feedback loop to GRPR versus other bombesin receptors untested
  14. 2023 Medium

    Microglial NLRP3/caspase-1/IL-1β signaling was shown to enhance GRPR+ neuron activation via IL-1R1 in chronic itch, revealing a neuroimmune amplification loop.

    Evidence NLRP3/caspase-1 inhibitors, Grpr-eGFP and Grpr KO mice, intrathecal IL-1β and IL-1R1 antagonist, RNAscope ISH

    PMID:36876522

    Open questions at the time
    • Whether IL-1β directly modulates GRPR expression or signaling efficiency unknown
    • Single lab study, not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of GRPR bound to GRP or antagonist is lacking, and the mechanisms by which GRPR+ spinal neurons differentially encode itch versus pain at the population level remain unresolved.
  • No cryo-EM or crystal structure of GRPR
  • Population coding logic of GRPR+ neurons for itch versus pain undefined
  • Therapeutic targeting of GRPR in chronic itch or organ inflammation lacks clinical trial data

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 8 R-HSA-112316 Neuronal System 3 R-HSA-168256 Immune System 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 1
Partners
HTR1AITPR3NMBROPRM1PIK3CGPLCB3TLR4

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 MOR1D heterodimerizes with GRPR in the spinal cord, and morphine triggers co-internalization of both MOR1D and GRPR, whereas GRP specifically triggers only GRPR internalization. This heterodimerization mediates opioid-induced itch via unidirectional cross-activation of GRPR signaling by MOR1D, downstream through PLCβ3 and IP3R3. Co-immunoprecipitation, receptor internalization assays, genetic and pharmacologic inhibition of PLCβ3/IP3R3, behavioral assays in knockout mice Cell High 22000021
2014 5-HT1A and GRPR form receptor heteromeric complexes in spinal cord neurons; co-activation of 5-HT1A and GRPR greatly potentiates subthreshold GRP-induced Ca2+ transients and action potential firing in GRPR+ neurons, establishing a descending serotonergic facilitation of GRP-GRPR itch signaling. Immunostaining, biochemical co-localization, biophysical/FRET studies, calcium imaging, pharmacological and behavioral screening Neuron High 25453842
2014 Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching, demonstrating that BNP-NPRA signaling does not function upstream of the GRP-GRPR dedicated neuronal pathway for itch. Pharmacological blockade, genetic knockout, intrathecal injection behavioral assays, in situ hybridization, RT-PCR Molecular pain Medium 24438367
2014 GRPR and NMBR cross-inhibit each other's signaling; in double-knockout mice lacking both Nmbr and Grpr, histaminergic itch is significantly reduced, demonstrating that GRPR and NMBR compensate for each other to maintain normal histamine-evoked itch. GRPR activity is enhanced in Nmbr KO mice and vice versa. GRP can signal through both GRPR and NMBR, while GRPR+ neurons act downstream of NMBR+ neurons in histaminergic itch circuits. Double knockout mice, single knockout mice behavioral assays, pharmacological scratching assays, GRPR expression analysis The Journal of neuroscience High 25209280
2011 GRPR mediates GRP-induced neutrophil chemotaxis; GRP-induced neutrophil migration in vitro is dependent on PLC-β2, PI3K, ERK, and p38 signaling, and is independent of Gαi protein. In vivo, GRP-induced peritoneal neutrophil recruitment is blocked by the GRPR antagonist RC-3095 and requires macrophages and TNF. In vivo peritoneal neutrophil recruitment assay, in vitro chemotaxis assay with pharmacological inhibitors, macrophage depletion, TNF neutralization Proceedings of the National Academy of Sciences of the United States of America High 22203955
2015 GRPR signals through the PI3Kγ/Akt pathway in spinal cord neurons; GRP directly activates small-size capsaicin-sensitive DRG neurons causing Ca2+ transients and membrane depolarization (~20 mV), and GRPR activation induces Akt phosphorylation in ex vivo spinal cords and in GRPR-transfected HEK293 cells. PI3Kγ inhibition reduces GRP-induced scratching. Electrophysiology (patch clamp), calcium imaging, Akt phosphorylation assay in ex vivo spinal cord and transfected HEK293 cells, intrathecal pharmacology, behavioral assays The Journal of neuroscience High 26658875
2019 Spinal GRPR+ neurons (excitatory interneurons) receive direct and indirect inputs from C and Aδ fibers and form contacts with NK1R-expressing projection neurons. Noxious or cooling agents inhibit GRPR neuron activity via GABAergic signaling; capsaicin enhances both excitatory and inhibitory spontaneous synaptic transmission onto GRPR neurons. Electrophysiology, immunohistochemistry, pharmacological manipulation (GABAergic), behavioral assays Scientific reports High 31676846
2019 Spinal galanin+ GABAergic neurons form inhibitory synapses with GRPR+ neurons and gate GRPR+-dependent itch signaling; spinal nNOS+ neurons also provide local inhibitory input to GRPR+ neurons; GRPR+ neurons additionally receive long-range inhibitory input from the rostral ventromedial medulla. Viral tracing, electrophysiology, immunohistochemistry, circuit dissection Proceedings of the National Academy of Sciences of the United States of America High 31806757
2004 Key amino acids in GRPR responsible for high-affinity GRP binding were identified; residues K101, Q121, A198, P199, S293, R288, and T297 are critical for GRP selectivity. Single and combined mutations in these residues reduce GRP affinity, and reverse mutations in BRS-3 confer GRP affinity gain. Site-directed mutagenesis, radioligand binding assays, chimeric receptor analysis, molecular modeling Biochemical pharmacology High 15670577
2013 GRP acts via postsynaptic BB2 (GRPR) receptors in rat paraventricular thalamic neurons to suppress a Ba2+-sensitive inward rectifier K+ conductance and activate a non-selective cation conductance with TRPV1-like biophysical and pharmacological properties, producing sustained membrane depolarization and burst/tonic firing. Perforated patch clamp electrophysiology in acute brain slices, pharmacological dissection with TRPV1 antagonists and BB2 antagonists The Journal of physiology High 23359674
2005 Brain GRPR (BB2 receptor)-mediated activation of sympatho-adrenomedullary outflow (plasma catecholamine release) in rats involves the PLC/diacylglycerol lipase signaling pathway rather than PLA2; GRP and bombesin (but not neuromedin B) elevate plasma catecholamines via BB2 receptors, and this is blocked by PLC and diacylglycerol lipase inhibitors. Intracerebroventricular injection, pharmacological inhibition of PLC/diacylglycerol lipase vs PLA2, plasma catecholamine measurement, receptor-subtype-selective antagonists European journal of pharmacology Medium 15910801
2016 GRPR activation by bombesin (BBN) in prostate cancer cells promotes epithelial-to-mesenchymal transition (EMT), upregulating TWIST, SNAIL, and SLUG mRNA while downregulating E-cadherin and β-catenin. GRPR activation also increases tumor cell proliferation, migration in vitro, and tumor growth and invasion in vivo; blockade of GRPR upregulates E-cadherin and downregulates VIMENTIN and SNAIL. Stable GRPr transfection in Ace-1 cells, proliferation assay, migration assay, bioluminescence tumor growth imaging, qRT-PCR for EMT markers, in vivo xenograft The Prostate Medium 26939805
2023 GRP/GRPR signaling enhances alcohol-associated liver injury through two distinct mechanisms: IRF1-mediated Caspase-1 inflammasome activation and NOX2-dependent reactive oxygen species production. GRPR interacts with TLR4 to activate STAT1, which binds promoters of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophage recruitment in acute kidney injury; STAT1 also induces GRP synthesis forming a positive feedback loop. Grpr knockout mice (global and conditional), GRPR overexpression, ChIP (STAT1 binding), co-immunoprecipitation (GRPR-TLR4 interaction), STAT1 overexpression rescue, pharmacological antagonist (RH-1402) Hepatology / Molecular therapy High 37409771 37415332
2020 GRPR and NPRA (natriuretic peptide receptor A) signaling activate ERK1/2 in spinal neurons as a critical downstream pathway for itch transmission; phosphorylated ERK is detected in interneurons expressing GRPR, NPRA, NMBR, and sst2A. Blocking GRPR by genetic approaches or toxins significantly attenuates spinal ERK phosphorylation. RNA sequencing, western blot for phospho-ERK, pharmacological/genetic GRPR blockade, HEK293T transfection with receptor agonist stimulation, chronic itch mouse models The Journal of investigative dermatology Medium 33039402
2000 GRP-R-deficient male mice display increased non-aggressive social responses and altered olfactory preference (preferring conspecific odors over their own), establishing a role for GRPR in modulating social investigatory behavior and conspecific odor cognition. Germline knockout mice, social interaction behavioral tests, olfactory preference tests, pharmacological (diazepam) controls Brain research Medium 10869497
2006 GRP-R immunoreactivity localizes to the plasma membrane of tumor cells, and receptor immunostaining undergoes translocation after bombesin (BN) exposure, confirming receptor internalization upon agonist binding. Antipeptide antibody development, Western blot, immunohistochemistry, transfected cell surface staining, ligand-induced internalization/translocation assay Virchows Archiv Medium 16967266
2023 GRP/GRPR promotes hyperuricemia-induced tubular injury by suppressing ABCG2/PDZK1 and increasing TGF-β/Smad3 via NF-κB pathway activation; GRPR knockout or conditional knockout in renal tubular epithelial cells protects against hyperuricemia-induced renal fibrosis and inflammation. GRPR knockout and conditional KO mice, RNA-seq, NF-κB inhibitor, GRPR overexpression in HK2 cells, GRPR antagonist RH-1402 treatment in vivo Biochemical pharmacology Medium 38084678
2023 Spinal microglia activate the NLRP3/caspase-1/IL-1β axis under chronic itch conditions, and IL-1β signals through IL-1R1 expressed on GRPR+ neurons to enhance their activation, establishing a microglia-GRPR+ neuron interaction axis in chronic itch. NLRP3/caspase-1 pharmacological blockade, Grpr-eGFP and Grpr KO mice, intrathecal IL-1β and IL-1R1 antagonist injection, RNAscope ISH, immunohistochemistry Allergy Medium 36876522
2022 GRPR+ neurons in the superficial dorsal horn are glutamatergic vertical cells concentrated in lamina I and outer lamina II; they receive monosynaptic input from Trpv1-expressing nociceptive afferents, respond to both noxious and pruritic stimuli, and their axons target projection neuron-containing regions. Chemogenetic activation produces both pain-related and itch-related behaviors. GRPR CreERT2 mouse line, viral tracing, immunohistochemistry, electrophysiology, DREADD-based chemogenetics, behavioral assays Pain High 35543635
1995 GRPR was mapped to the Xp22.1-p22.2 region of the human X chromosome, localized between DXS43 and CALB3, establishing its chromosomal position. YAC contig construction, STS mapping, restriction mapping Genomics Medium 7759104

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Unidirectional cross-activation of GRPR by MOR1D uncouples itch and analgesia induced by opioids. Cell 210 22000021
2010 Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. European journal of nuclear medicine and molecular imaging 164 20717822
2006 177Lu-AMBA: Synthesis and characterization of a selective 177Lu-labeled GRP-R agonist for systemic radiotherapy of prostate cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 164 16818949
2009 (68)Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging. European journal of nuclear medicine and molecular imaging 120 19360404
2016 68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 103 27609789
2014 Preclinical evaluation of a bispecific low-molecular heterodimer targeting both PSMA and GRPR for improved PET imaging and therapy of prostate cancer. The Prostate 95 24464532
2013 Targeting GRPR in urological cancers--from basic research to clinical application. Nature reviews. Urology 95 23507930
2014 Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling. Neuron 94 25453842
2017 PET Using a GRPR Antagonist 68Ga-RM26 in Healthy Volunteers and Prostate Cancer Patients. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 89 29123014
2013 Synthesis and characterization of a high-affinity NOTA-conjugated bombesin antagonist for GRPR-targeted tumor imaging. Bioconjugate chemistry 71 23763444
2011 F-Labeled GRPR Agonists and Antagonists: A Comparative Study in Prostate Cancer Imaging. Theranostics 70 21544226
2011 Gastrin-releasing peptide receptor (GRPR) mediates chemotaxis in neutrophils. Proceedings of the National Academy of Sciences of the United States of America 67 22203955
2018 68Ga-BBN-RGD PET/CT for GRPR and Integrin αvβ3 Imaging in Patients with Breast Cancer. Theranostics 65 29464003
2009 177Lu-AMBA biodistribution, radiotherapeutic efficacy, imaging, and autoradiography in prostate cancer models with low GRP-R expression. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 64 19910427
2019 Comparative Study of Subcutaneous and Orthotopic Mouse Models of Prostate Cancer: Vascular Perfusion, Vasculature Density, Hypoxic Burden and BB2r-Targeting Efficacy. Scientific reports 58 31366895
2018 Prospective Study of the Radiolabeled GRPR Antagonist BAY86-7548 for Positron Emission Tomography/Computed Tomography Imaging of Newly Diagnosed Prostate Cancer. European urology oncology 58 31017093
2014 B-type natriuretic peptide is neither itch-specific nor functions upstream of the GRP-GRPR signaling pathway. Molecular pain 58 24438367
2016 Novel Bispecific PSMA/GRPr Targeting Radioligands with Optimized Pharmacokinetics for Improved PET Imaging of Prostate Cancer. Bioconjugate chemistry 56 26726823
2021 PSMA- and GRPR-Targeted PET: Results from 50 Patients with Biochemically Recurrent Prostate Cancer. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 53 33674398
2014 Cross-inhibition of NMBR and GRPR signaling maintains normal histaminergic itch transmission. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 25209280
2019 Synaptic control of spinal GRPR+ neurons by local and long-range inhibitory inputs. Proceedings of the National Academy of Sciences of the United States of America 46 31806757
1998 PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist. Bioorganic & medicinal chemistry letters 46 9873586
2021 Exosomes Isolated From Bone Marrow Mesenchymal Stem Cells Exert a Protective Effect on Osteoarthritis via lncRNA LYRM4-AS1-GRPR-miR-6515-5p. Frontiers in cell and developmental biology 44 34124036
2014 PSMA, EpCAM, VEGF and GRPR as imaging targets in locally recurrent prostate cancer after radiotherapy. International journal of molecular sciences 44 24727373
2019 Bispecific GRPR-Antagonistic Anti-PSMA/GRPR Heterodimer for PET and SPECT Diagnostic Imaging of Prostate Cancer. Cancers 42 31540122
2020 Peptide-Conjugated Long-Lived Theranostic Imaging for Targeting GRPr in Cancer and Immune Cells. Angewandte Chemie (International ed. in English) 41 32649787
2014 Synthesis and biological evaluation of copper-64 radiolabeled [DUPA-6-Ahx-(NODAGA)-5-Ava-BBN(7-14)NH2], a novel bivalent targeting vector having affinity for two distinct biomarkers (GRPr/PSMA) of prostate cancer. Nuclear medicine and biology 40 24508213
2019 Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord. Scientific reports 38 31676846
2013 A heterodimeric [RGD-Glu-[(64)Cu-NO2A]-6-Ahx-RM2] αvβ3/GRPr-targeting antagonist radiotracer for PET imaging of prostate tumors. Nuclear medicine and biology 38 24480266
2021 GRPr Antagonist 68Ga-SB3 PET/CT Imaging of Primary Prostate Cancer in Therapy-Naïve Patients. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 37 33789933
2013 In vitro and in vivo evaluation of a (18)F-labeled high affinity NOTA conjugated bombesin antagonist as a PET ligand for GRPR-targeted tumor imaging. PloS one 37 24312607
2012 Immunohistochemical analysis of gastrin-releasing peptide receptor (GRPR) and possible regulation by estrogen receptor βcx in human prostate carcinoma. Neoplasma 37 22248281
2021 Magnetic and GRPR-targeted reduced graphene oxide/doxorubicin nanocomposite for dual-targeted chemo-photothermal cancer therapy. Materials science & engineering. C, Materials for biological applications 33 34474862
1998 Identification and location on syndecan-1 core protein of the epitopes of B-B2 and B-B4 monoclonal antibodies. FEBS letters 33 9598980
2020 Spinal GRPR and NPRA Contribute to Chronic Itch in a Murine Model of Allergic Contact Dermatitis. The Journal of investigative dermatology 31 32032577
1995 A 6-Mb YAC contig in Xp22.1-p22.2 spanning the DXS69E, XE59, GLRA2, PIGA, GRPR, CALB3, and PHKA2 genes. Genomics 31 7759104
2019 Comparison of the binding of the gastrin-releasing peptide receptor (GRP-R) antagonist 68Ga-RM2 and 18F-FDG in breast cancer samples. PloS one 30 30645633
2009 BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells. Journal of molecular neuroscience : MN 30 19642024
2023 Microglia-neuron interactions promote chronic itch via the NLRP3-IL-1β-GRPR axis. Allergy 29 36876522
2023 GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway. Hepatology (Baltimore, Md.) 29 37409771
2016 Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer. The Prostate 29 26939805
2014 PESIN multimerization improves receptor avidities and in vivo tumor targeting properties to GRPR-overexpressing tumors. Bioconjugate chemistry 29 24533789
2020 Heterodimeric Radiotracer Targeting PSMA and GRPR for Imaging of Prostate Cancer-Optimization of the Affinity towards PSMA by Linker Modification in Murine Model. Pharmaceutics 28 32630176
2019 Comparison of the radiolabeled PSMA-inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2 in primary prostate cancer samples. EJNMMI research 28 31161459
2017 High Contrast PET Imaging of GRPR Expression in Prostate Cancer Using Cobalt-Labeled Bombesin Antagonist RM26. Contrast media & molecular imaging 28 29097932
2016 Pre-clinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors. EJNMMI research 28 26897133
2015 GRPR/PI3Kγ: Partners in Central Transmission of Itch. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 26658875
2023 Novel insight on GRP/GRPR axis in diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 36933382
2022 Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain. Pain 27 35543635
2017 Characterization of NMB, GRP and their receptors (BRS3, NMBR and GRPR) in chickens. Journal of molecular endocrinology 27 28500250
2017 NeoBOMB1, a GRPR-Antagonist for Breast Cancer Theragnostics: First Results of a Preclinical Study with [67Ga]NeoBOMB1 in T-47D Cells and Tumor-Bearing Mice. Molecules (Basel, Switzerland) 27 29137110
2014 A new (68)Ga-labeled BBN peptide with a hydrophilic linker for GRPR-targeted tumor imaging. Amino acids 27 24633452
2021 [99mTc]Tc-DB15 in GRPR-Targeted Tumor Imaging with SPECT: From Preclinical Evaluation to the First Clinical Outcomes. Cancers 26 34680243
2010 In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors. Bioconjugate chemistry 26 20857927
2023 Phase I Trial of [99mTc]Tc-maSSS-PEG2-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors. Cancers 25 36980517
2019 Synthesis and Preclinical Evaluation of Radio-Iodinated GRPR/PSMA Bispecific Heterodimers for the Theranostics Application in Prostate Cancer. Pharmaceutics 25 31340483
2006 Immunohistochemical detection of bombesin receptor subtypes GRP-R and BRS-3 in human tumors using novel antipeptide antibodies. Virchows Archiv : an international journal of pathology 25 16967266
2000 Male mice lacking the gastrin-releasing peptide receptor (GRP-R) display elevated preference for conspecific odors and increased social investigatory behaviors. Brain research 25 10869497
2023 GRPR-targeting radiotheranostics for breast cancer management. Frontiers in medicine 24 38020178
2004 Identification of key amino acids in the gastrin-releasing peptide receptor (GRPR) responsible for high affinity binding of gastrin-releasing peptide (GRP). Biochemical pharmacology 24 15670577
2013 Gastrin-releasing peptide acts via postsynaptic BB2 receptors to modulate inward rectifier K+ and TRPV1-like conductances in rat paraventricular thalamic neurons. The Journal of physiology 23 23359674
1998 Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes. Genomics 23 9479493
2023 Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates. International journal of molecular sciences 22 36834815
2023 Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis. Molecular therapy : the journal of the American Society of Gene Therapy 22 37415332
2019 Selection of an optimal macrocyclic chelator improves the imaging of prostate cancer using cobalt-labeled GRPR antagonist RM26. Scientific reports 22 31745219
2015 GRPR-targeted Protein Contrast Agents for Molecular Imaging of Receptor Expression in Cancers by MRI. Scientific reports 22 26577829
2016 Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer. Bioconjugate chemistry 21 27399868
2014 Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors. Journal of medicinal chemistry 21 25474596
1996 Efficacy and toxicity of plasma-cell-reactive monoclonal antibodies B-B2 and B-B4 and their immunotoxins. Cancer immunology, immunotherapy : CII 21 8830734
2024 IL-6 Enhances the Activation of PI3K-AKT/mTOR-GSK-3β by Upregulating GRPR in Hippocampal Neurons of Autistic Mice. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 20 38536552
1993 Comparative mapping of the Grpr locus on the X chromosomes of man and mouse. Genomics 20 8406441
2023 Preclinical Comparison of the 64Cu- and 68Ga-Labeled GRPR-Targeted Compounds RM2 and AMTG, as Well as First-in-Humans [68Ga]Ga-AMTG PET/CT. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 19 37934025
2021 GRPr-mediated photothermal and thermodynamic dual-therapy for prostate cancer with synergistic anti-apoptosis mechanism. Nanoscale 19 33595022
2021 In Vivo Biodistribution and Efficacy Evaluation of NeoB, a Radiotracer Targeted to GRPR, in Mice Bearing Gastrointestinal Stromal Tumor. Cancers 19 33801382
2013 Preclinical evaluation of a novel ¹¹¹In-labeled bombesin homodimer for improved imaging of GRPR-positive prostate cancer. Molecular pharmaceutics 19 23590837
2024 Gastrin-releasing peptide receptor (GRPR) as a novel biomarker and therapeutic target in prostate cancer. Annals of medicine 18 38442298
2022 68Ga-Labeled [Leu13ψThz14]Bombesin(7-14) Derivatives: Promising GRPR-Targeting PET Tracers with Low Pancreas Uptake. Molecules (Basel, Switzerland) 18 35744904
2020 Characterization of the Fe metalloproteome of a ubiquitous marine heterotroph, Pseudoalteromonas (BB2-AT2): multiple bacterioferritin copies enable significant Fe storage. Metallomics : integrated biometal science 18 32301469
2020 GRPR/Extracellular Signal-Regulated Kinase and NPRA/Extracellular Signal-Regulated Kinase Signaling Pathways Play a Critical Role in Spinal Transmission of Chronic Itch. The Journal of investigative dermatology 18 33039402
2012 Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells. Molecular and clinical oncology 18 24649138
2024 Lower-grade gliomas surgery guided by GRPR-targeting PET/NIR dual-modality image probe: a prospective and single-arm clinical trial. Theranostics 17 38169486
2021 Development of Heterobivalent Theranostic Probes Having High Affinity/Selectivity for the GRPR/PSMA. Journal of medicinal chemistry 17 33534560
2012 Evaluation of a technetium-99m labeled bombesin homodimer for GRPR imaging in prostate cancer. Amino acids 17 22833158
2009 Association and linkage analysis of candidate genes GRP, GRPR, CRHR1, and TACR1 in panic disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 17 18452185
2024 Synthesis, preclinical, and initial clinical evaluation of integrin αVβ3 and gastrin-releasing peptide receptor (GRPR) dual-targeting radiotracer [68Ga]Ga-RGD-RM26-03. European journal of nuclear medicine and molecular imaging 16 38376806
2020 Functional Hybrid Molecules for the Visualization of Cancer: PESIN-Homodimers Combined with Multimodal Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging: Suited for Tracking of GRPR-Positive Malignant Tissue*. Chemistry (Weinheim an der Bergstrasse, Germany) 16 32618007
2019 68Ga-NOTA-Aca-BBN(7-14) PET imaging of GRPR in children with optic pathway glioma. European journal of nuclear medicine and molecular imaging 16 31270559
2017 GRPR antagonist protects from drug-induced liver injury by impairing neutrophil chemotaxis and motility. European journal of immunology 16 28294319
2014 The Gastrin-Releasing Peptide Receptor (GRPR) in the Spinal Cord as a Novel Pharmacological Target. Current neuropharmacology 16 25426011
2021 100 Hz Electroacupuncture Alleviated Chronic Itch and GRPR Expression Through Activation of Kappa Opioid Receptors in Spinal Dorsal Horn. Frontiers in neuroscience 15 33664646
2020 GRPR-targeted SPECT imaging using a novel bombesin-based peptide for colorectal cancer detection. Biomaterials science 15 33140758
2021 Preclinical Evaluation of 99mTc-Labeled GRPR Antagonists maSSS/SES-PEG2-RM26 for Imaging of Prostate Cancer. Pharmaceutics 14 33573232
2020 Development and Preclinical Evaluation of 99mTc- and 186Re-Labeled NOTA and NODAGA Bioconjugates Demonstrating Matched Pair Targeting of GRPR-Expressing Tumors. Molecular imaging and biology 14 32886303
2017 Amide-to-triazole switch vs. in vivo NEP-inhibition approaches to promote radiopeptide targeting of GRPR-positive tumors. Nuclear medicine and biology 14 28636973
2017 Evaluation of a novel GRPR antagonist for prostate cancer PET imaging: [64Cu]-DOTHA2-PEG-RM26. Nuclear medicine and biology 14 29154145
2001 Discovery of potent and selective peptide agonists at the GRP-preferring bombesin receptor (BB2). Journal of peptide science : an official publication of the European Peptide Society 14 11763364
2023 Antipruritic effects of geraniol on acute and chronic itch via modulating spinal GABA/GRPR signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 13 37516088
2023 GRP/GRPR signaling pathway aggravates hyperuricemia-induced renal inflammation and fibrosis via ABCG2-dependent mechanisms. Biochemical pharmacology 13 38084678
2021 66Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [66Ga]Ga-NOTA-PEG2-RM26. Scientific reports 13 33574368
2005 Brain phospholipase C/diacylglycerol lipase are involved in bombesin BB2 receptor-mediated activation of sympatho-adrenomedullary outflow in rats. European journal of pharmacology 13 15910801