Affinage

GRPR

Gastrin-releasing peptide receptor · UniProt P30550

Length
384 aa
Mass
43.2 kDa
Annotated
2026-06-10
100 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRPR is a plasma-membrane G protein-coupled receptor for gastrin-releasing peptide (GRP) that serves as a central transmitter of itch in the spinal cord and as a driver of inflammation, necroptosis, and fibrosis in peripheral epithelial and immune tissues (PMID:35543635, PMID:37415332). In the superficial dorsal horn, GRPR marks a population of glutamatergic vertical interneurons concentrated in laminae I–II that receive monosynaptic input from TRPV1+ nociceptors, contact NK1R+ projection neurons, and respond to both pruritic and noxious stimuli (PMID:35543635, PMID:31676846). Upon GRP binding—mediated by an inward-facing residue cluster including K101, Q121, R288, and S293 in the ligand pocket (PMID:15670577)—activated GRPR depolarizes neurons and signals through PLCβ3/IP3R3, PI3Kγ/Akt, and ERK1/2 cascades to transmit itch (PMID:22000021, PMID:26658875, PMID:33039402). Receptor function is tuned by heteromerization: GRPR forms a complex with the μ-opioid receptor isoform MOR1D that cross-activates GRPR to produce opioid-induced itch without affecting analgesia (PMID:22000021), and with 5-HT1A to potentiate subthreshold GRP responses under descending serotonergic drive (PMID:25453842). GRPR+ neuron output is gated by local galanin+ and nNOS+ GABAergic interneurons and by long-range inhibitory inputs from the rostral ventromedial medulla, and is amplified by microglial NLRP3/caspase-1/IL-1β signaling acting through IL-1R1 on GRPR+ neurons in chronic itch (PMID:31806757, PMID:36876522). GRPR also partially overlaps functionally with NMBR in histaminergic itch (PMID:25209280). In peripheral disease, GRPR physically interacts with TLR4 to activate STAT1, driving MLKL/CCL2-dependent tubular necroptosis and a GRP/GRPR/STAT1 feedforward loop in acute kidney injury (PMID:37415332), and engages IRF1/caspase-1 inflammasome and NOX2/ROS pathways in myeloid cells in alcohol-associated liver injury (PMID:37409771) and NF-κB/TGF-β/Smad3 signaling in hyperuricemic nephropathy (PMID:38084678). Beyond these roles, GRPR agonism promotes EMT and tumor growth in prostate cancer cells (PMID:26939805), and GRPR knockout mice show deficits in fear extinction and altered social investigatory behavior (PMID:22312434, PMID:10869497).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 Medium

    Whether GRPR has functions in the brain beyond peptide signaling was addressed by phenotyping knockout mice, revealing a role in social and chemosensory behavior.

    Evidence GRPR knockout mice in resident-intruder, social investigation, and olfactory preference tests

    PMID:10869497

    Open questions at the time
    • Circuit and molecular mechanism linking GRPR to social behavior not defined
    • Brain region of action not localized
  2. 2004 High

    The structural basis of GRP recognition was unknown; systematic mutagenesis mapped the residues conferring high-affinity, selective GRP binding.

    Evidence Site-directed mutagenesis of 14 single and combination mutants with radioligand binding and reciprocal gain-of-affinity mutations in BRS-3

    PMID:15670577

    Open questions at the time
    • No experimental three-dimensional structure of the GRPR-GRP complex
    • Residues governing G protein coupling not addressed
  3. 2006 Medium

    Receptor trafficking behavior was clarified by showing plasma-membrane localization and agonist-induced internalization, supporting ligand-targeted imaging strategies.

    Evidence Western blot, immunostaining, and bombesin-induced translocation in tumor cells; radioligand binding/internalization with 177Lu-AMBA in PC-3 cells

    PMID:16818949 PMID:16967266

    Open questions at the time
    • Internalization machinery and recycling fate not characterized
    • Quantitative kinetics restricted to tumor cell lines
  4. 2011 High

    How opioids trigger itch was resolved by showing a MOR1D-GRPR heterodimer that cross-activates GRPR/PLCβ3/IP3R3, dissociating itch from analgesia.

    Evidence Reciprocal Co-IP, internalization assays, PLCβ3/IP3R3 knockdown, pharmacology, and behavior in mice

    PMID:22000021

    Open questions at the time
    • Stoichiometry and structural interface of the heterodimer unknown
    • Whether the heterodimer operates outside the spinal cord not tested
  5. 2011 High

    A peripheral, non-neuronal role for GRPR was established by demonstrating it drives GRP-induced neutrophil chemotaxis through a defined kinase cascade.

    Evidence In vivo peritoneal recruitment and in vitro chemotaxis with PLC-β2/PI3K/ERK/p38 inhibitors and GRPR antagonist RC-3095

    PMID:22203955

    Open questions at the time
    • G protein coupling identity left open (shown Gi-independent)
    • In vivo contribution to specific inflammatory diseases not yet mapped
  6. 2012 Medium

    GRPR's CNS role was extended to emotional learning and its transcriptional control was probed, linking it to amygdala-prefrontal circuit balance and estrogen receptor regulation.

    Evidence GRPR KO mice in fear extinction with c-Fos mapping; ERβcx overexpression in PC-3 cells with RT-PCR and human tissue correlation; X-inactivation mapping in a translocation patient

    PMID:22248281 PMID:22312434 PMID:9259269

    Open questions at the time
    • Direct transcriptional mechanism of ERβcx on GRPR promoter not shown
    • Causal link between GRPR circuit changes and extinction behavior is correlative (c-Fos)
  7. 2014 High

    The spinal itch circuit was defined: GRPR+ neurons are excitatory interneurons integrating afferent input, gated by GABA, with NMBR providing partial redundancy in histaminergic itch.

    Evidence Patch-clamp of identified GRPR neurons with GABAergic blockade; single and double Nmbr/Grpr knockout mice across pruritogen paradigms

    PMID:25209280 PMID:31676846

    Open questions at the time
    • Molecular basis of GRP cross-signaling to NMBR not resolved
    • How noxious versus pruritic inputs are discriminated by these neurons unclear
  8. 2014 High

    GRPR signal facilitation and effector pathways were defined: 5-HT1A heteromerization potentiates GRP responses, and PI3Kγ/Akt is required for itch transmission, while BNP-NPRA is not upstream.

    Evidence Co-IP/Ca2+ imaging/electrophysiology for 5-HT1A; ex vivo Akt phosphorylation, HEK293 transfection, PI3Kγ inhibition and behavior; genetic/pharmacological BNP epistasis

    PMID:24438367 PMID:25453842 PMID:26658875

    Open questions at the time
    • Interface and stoichiometry of the 5-HT1A-GRPR heteromer not defined
    • Relative contribution of PI3Kγ/Akt versus PLC and ERK arms not quantified
  9. 2016 High

    An oncogenic function was established by showing GRPR agonism drives EMT, proliferation, and invasion in prostate cancer, reversible by GRPR blockade.

    Evidence Stable GRPr transfection of Ace-1 cells with proliferation/migration assays, EMT marker RT-PCR, and in vivo tumor models

    PMID:26939805

    Open questions at the time
    • Intracellular signaling pathway coupling GRPR to EMT transcription factors not delineated
    • Endogenous ligand source in the tumor microenvironment unknown
  10. 2020 High

    The identity and connectivity of spinal GRPR+ neurons and their dominant signaling output were resolved, defining them as nociceptor-innervated vertical cells signaling through ERK1/2.

    Evidence GRPR-CreERT2 mice with viral tracing, electrophysiology, chemogenetics; RNA-seq and pERK western blot in itch models plus GRPR-HEK293T signaling

    PMID:33039402 PMID:35543635

    Open questions at the time
    • How a single population encodes both pain and itch is unresolved
    • Hierarchy among PLCβ, PI3Kγ, and ERK arms in vivo not established
  11. 2023 High

    Top-down and bottom-up control of GRPR+ neurons in chronic itch was mapped, identifying inhibitory gating circuits and microglial inflammasome-driven facilitation.

    Evidence Viral tracing/electrophysiology of galanin+/nNOS+/RVM inputs; Grpr reporter and KO mice with NLRP3/caspase-1/IL-1R1 pharmacology and intrathecal IL-1β

    PMID:31806757 PMID:36876522

    Open questions at the time
    • Conditions selecting disinhibition versus microglial facilitation not defined
    • Direct synaptic versus diffusible action of microglial IL-1β not fully separated
  12. 2023 High

    GRPR's peripheral pathogenic role was mechanistically expanded across organs, defining receptor-TLR4 coupling and distinct downstream inflammatory effectors in kidney and liver injury.

    Evidence GRPR-TLR4 Co-IP and STAT1 ChIP with global/conditional Grpr KO in AKI; myeloid-specific KO with IRF1/caspase-1 and NOX2 readouts in liver injury; tubular-specific KO with NF-κB/TGF-β/Smad3 in hyperuricemic nephropathy

    PMID:37409771 PMID:37415332 PMID:38084678

    Open questions at the time
    • Whether GRPR-TLR4 forms a direct stable complex or transient assembly is unresolved
    • Source and regulation of local GRP ligand in each disease not fully defined
  13. 2024 Medium

    A cytokine-driven CNS signaling link was identified, with IL-6 upregulating GRPR to engage PI3K-AKT/mTOR-GSK-3β in hippocampal neurons.

    Evidence Maternal immune activation model with GRPR knockdown in HT22 cells, IL-6 treatment, and pathway western blots

    PMID:38536552

    Open questions at the time
    • Mechanism of IL-6-driven GRPR transcriptional upregulation not defined
    • Behavioral consequence of hippocampal GRPR signaling not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A unified picture of how GRPR's G protein coupling and effector arm selection (PLCβ/IP3R3 vs PI3Kγ/Akt vs ERK) is biased across neuronal versus immune/epithelial contexts, and the structural basis of its heteromeric and TLR4 partnerships, remains open.
  • No experimental GRPR structure or activation-state model
  • Mechanism dictating context-specific effector selection unknown
  • Direct versus indirect nature of GRPR-TLR4 interaction unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3
Partners
HTR1AMOR1DNMBRTLR4

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 MOR1D (a μ-opioid receptor isoform) heterodimerizes with GRPR in the spinal cord, and morphine triggers internalization of both GRPR and MOR1D together, whereas GRP specifically triggers only GRPR internalization. This MOR1D-GRPR heterodimer mediates opioid-induced itch via unidirectional cross-activation of GRPR signaling; blocking MOR1D-GRPR association attenuates morphine-induced scratching but not analgesia. Downstream effectors PLCβ3 and IP3R3 are required for this GRPR-mediated itch pathway. Co-immunoprecipitation (heterodimer identification), internalization assays, pharmacological and molecular inhibition (PLCβ3, IP3R3 knockdown), behavioral assays in mice Cell High 22000021
2014 5-HT1A receptor and GRPR form receptor heteromeric complexes in the spinal cord. Coactivation of 5-HT1A and GRPR greatly potentiates subthreshold GRP-induced Ca2+ transients and action potential firing of GRPR+ neurons, providing a mechanism by which the descending serotonergic system facilitates itch transmission via GRP-GRPR signaling. Immunostaining, biochemical co-immunoprecipitation, biophysical studies, electrophysiology (calcium imaging, action potential recording), pharmacological and behavioral assays Neuron High 25453842
2014 GRPR-expressing spinal neurons are excitatory interneurons that receive direct and indirect synaptic inputs from C and Aδ fibers and form contacts with NK1R-expressing projection neurons. Noxious stimuli and cooling inhibit GRPR neuron activity via GABAergic signaling, whereas capsaicin enhances both excitatory and inhibitory synaptic transmission onto GRPR neurons. Electrophysiology (patch-clamp recording of synaptic inputs), immunohistochemistry, pharmacological inhibition (GABAergic blockade), behavioral assays Scientific reports High 31676846
2014 NMBR and GRPR mutually compensate for each other in histaminergic itch: mice lacking both NMBR and GRPR (DKO) show significant deficits in histaminergic itch, while GRPR alone is required for chloroquine-evoked (nonhistaminergic) itch. GRP can signal through both GRPR and NMBR (albeit weakly to NMBR), whereas NMB signals exclusively through NMBR. GRPR+ neurons act downstream of NMBR+ neurons to integrate histaminergic itch information. Knockout mice (Nmbr-/-, Grpr-/-, double KO), intradermal pruritogen injection behavioral assays, pharmacological analysis The Journal of neuroscience High 25209280
2014 GRPR signals through the PI3Kγ/Akt pathway for itch transmission. GRP directly activates small-size capsaicin-sensitive DRG neurons causing calcium flux and ~20 mV membrane depolarization. GRPR activation induces Akt phosphorylation in ex vivo spinal cord and in GRPR-transfected HEK293 cells. PI3Kγ inhibition reduces GRP-induced scratching and reverses dry skin itch. Electrophysiology (calcium imaging, membrane potential recording), ex vivo spinal cord Akt phosphorylation assay, GRPR-transfected HEK293 cells, intrathecal injections, pharmacological inhibition, behavioral assays The Journal of neuroscience High 26658875
2014 Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching behavior, demonstrating that BNP-NPRA signaling is not upstream of the GRP-GRPR pathway in itch transmission. Pharmacological blockade, genetic knockout of Grpr, intrathecal BNP injection, scratching behavioral assay Molecular pain Medium 24438367
2011 GRPR mediates GRP-induced neutrophil chemotaxis in vivo. In vitro, GRP-induced neutrophil migration is dependent on PLC-β2, PI3K, ERK, and p38 signaling, and is independent of Gαi protein. In vivo peritoneal neutrophil recruitment assay (i.p. GRP injection, macrophage depletion, TNF neutralization), in vitro chemotaxis assay with pathway inhibitors (PLC-β2, PI3K, ERK, p38), GRPR antagonist RC-3095 blockade Proceedings of the National Academy of Sciences of the United States of America High 22203955
2016 GRPr agonist bombesin (BBN) promotes epithelial-to-mesenchymal transition (EMT) in prostate cancer cells, upregulating EMT markers (TWIST, SNAIL, SLUG) and downregulating epithelial markers (E-cadherin, β-catenin). BBN increased tumor cell proliferation, migration in vitro, and tumor growth and invasion in vivo. GRPr blockade reversed these effects. Stable transfection of GRPr into Ace-1 canine prostate cancer cells, cell proliferation assay, migration assay, bioluminescence tumor growth imaging, quantitative RT-PCR for EMT markers, in vivo subcutaneous and intratibial tumor models The Prostate High 26939805
2004 Key amino acids in GRPR responsible for high-affinity GRP binding were identified by mutagenesis: K101, Q121, A198, P199, S293, R288, T297 are particularly important for GRP selectivity. Combinations of mutations produced greater decreases in GRP affinity than single mutations. Reverse mutations in BRS-3 (making GRP gain-of-affinity mutants) confirmed these results. Modeling showed these residues have side chains oriented inward within 6Å of the binding pocket. Site-directed mutagenesis of GRPR (14 single mutants + combination mutants), radioligand binding assays, reverse mutations in BRS-3, molecular modeling Biochemical pharmacology High 15670577
2006 GRP-R protein localizes predominantly to the plasma membrane in human tumor cells; after bombesin exposure, GRP-R immunostaining translocates (receptor internalization), confirming agonist-induced internalization. Receptor is detected at Mr 50,000–70,000 on Western blot and at cell surface in transfected cells. Western blot of receptor-expressing membrane fractions, immunostaining of transfected cells, receptor translocation assay after bombesin exposure, antibody preadsorbtion controls Virchows Archiv Medium 16967266
2012 GRPR knockout mice display impaired cued fear extinction (slower extinction than wildtype), accompanied by increased c-Fos activity in the basolateral amygdala and decreased c-Fos activity in the prefrontal cortex during extinction, identifying GRPR as a regulator of amygdala-prefrontal circuit balance during fear extinction. GRPR knockout mice, cued and contextual fear conditioning/extinction behavioral paradigm, c-Fos immunostaining as indirect neuronal activity marker PloS one Medium 22312434
2000 GRP-R knockout male mice exhibit increased non-aggressive social responses and altered conspecific odor preference (preferring other males' odor over their own, opposite to wildtype), indicating GRPR regulates social investigatory behavior and chemosensory cognition in mice. GRP-R knockout mice, social interaction test (resident-intruder), social investigation test toward anesthetized conspecific, olfactory preference test, diazepam control Brain research Medium 10869497
2019 Spinal GRPR+ neurons receive inhibitory synaptic inputs from local galanin+ GABAergic neurons and local nNOS-expressing neurons, and also receive strong inhibitory inputs from the rostral ventromedial medulla (long-range). These inhibitory circuits gate GRPR+ neuron-dependent itch signaling. Viral tracing (circuit mapping), electrophysiology (patch-clamp), immunohistochemistry, Grpr-eGFP reporter mice Proceedings of the National Academy of Sciences of the United States of America High 31806757
2023 GRPR interacts with Toll-like receptor 4 to activate STAT1, which binds the promoters of MLKL and CCL2 to induce tubular epithelial cell necroptosis, necroinflammation, and macrophage recruitment in acute kidney injury. STAT1 also induces GRP synthesis, creating a GRP/GRPR/STAT1 positive feedback loop. Histone deacetylase 8 may drive GRPR transcriptional activation. Co-immunoprecipitation (GRPR-TLR4 interaction), STAT1 ChIP (promoter binding), Grpr knockout mice, tubular-specific Grpr conditional knockout (GRPRFlox/Flox/KspCre), STAT1 overexpression rescue, GRPR antagonist RH-1402 treatment, cisplatin and ischemia AKI models Molecular therapy High 37415332
2023 GRP/GRPR signaling in macrophages/neutrophils promotes alcohol-associated liver injury via two parallel mechanisms: IRF1-mediated Caspase-1 inflammasome activation and NOX2-dependent reactive oxygen species production. Histone H3 lysine 27 acetylation induced by alcohol promotes GRP expression, and GRP then binds GRPR to activate these pathways. Grpr-/- mice, Grprflox/floxLysMCre (myeloid-specific conditional KO) mice, GRPR overexpression, GRPR antagonist RH-1402, chromatin/histone modification analysis, inflammatory cytokine/chemokine measurement, serum biomarkers Hepatology High 37409771
2023 GRP/GRPR signaling promotes hyperuricemia-induced renal inflammation and fibrosis by activating NF-κB, which suppresses ABCG2/PDZK1 and increases TGF-β/Smad3 levels. GRPR conditional knockout in renal tubular epithelial cells (GRPRFlox/Flox/KspCre) protected mice from hyperuricemic nephropathy. Renal tubular epithelial cell-specific conditional KO (GRPRFlox/Flox/KspCre), global GRPR KO, RNA-seq, GRPR overexpression in HK2 cells, NF-κB inhibitor rescue, GRPR antagonist RH-1402, ELISA, immunohistochemistry Biochemical pharmacology High 38084678
2020 GRPR-expressing spinal neurons are identified as vertical cells (glutamatergic interneurons concentrated in lamina I and outer lamina II), accounting for ~15% of excitatory neurons in the superficial dorsal horn. Their axons target GRPR+ neurons themselves, lamina I NK1R projection neurons, lateral spinal nucleus, and lateral lamina V. Most GRPR cells receive monosynaptic input from Trpv1-expressing nociceptive afferents and respond to both noxious and pruritic stimuli. Chemogenetic activation produces both pain- and itch-related behaviors. GRPR-CreERT2 mouse line (conditional genetic targeting), viral tracing, electrophysiology, immunohistochemistry, RNAscope in situ hybridization, chemogenetics (DREADDs), behavioral assays Pain High 35543635
2023 Spinal microglia NLRP3/caspase-1/IL-1β axis promotes activation of GRPR+ neurons via IL-1R1, which is expressed on GRPR+ neurons. IL-1β+ microglia localize in close proximity to GRPR+ neurons, and intrathecal IL-1β enhances GRPR+ neuron activation, while IL-1R1 antagonist attenuates chronic itch. Grpr-eGFP and Grpr KO mice, immunohistochemistry, RNAscope ISH, pharmacological blockade (NLRP3, caspase-1, IL-1R1 antagonist), intrathecal IL-1β injection, western blot, behavioral assays, RNA sequencing Allergy High 36876522
2020 GRPR (and NPRA) downstream ERK1/2 phosphorylation is the most significantly upregulated signaling cascade in spinal cord during chronic itch. Phosphorylated ERK is detected in GRPR+ interneurons. Genetic blockade of GRPR significantly attenuates spinal ERK phosphorylation. In HEK293T cells transfected with GRPR, GRP activates ERK as the most prominent intracellular signaling molecule. RNA sequencing (spinal cord), western blot (pERK), MAPK/ERK kinase inhibitors, Grpr KO mice, GRPR-transfected HEK293T cells + GRP stimulation, RNAscope, behavioral assays The Journal of investigative dermatology High 33039402
1997 The GRPR gene on the X chromosome was shown to escape X-inactivation, as established by molecular analysis of a patient with an X;8 translocation whose breakpoint occurred in the first intron of GRPR. Molecular analysis of X;8 translocation patient, YAC and cosmid cloning, X-inactivation analysis Human molecular genetics Medium 9259269
2006 177Lu-AMBA (a radiolabeled bombesin analog) binds to GRP-R with high affinity (Kd = 1.02 nmol/L) and is internalized by GRP-R-expressing PC-3 cells (76.8% internalization), with markedly lower efflux (2.9%) compared to other analogs. Radioligand binding assay (Kd, Bmax determination), internalization and efflux assays in PC-3 cells, receptor autoradiography Journal of nuclear medicine Medium 16818949
2012 ERβcx (an estrogen receptor β splice variant) regulates GRPR expression in prostate cancer cells: stable overexpression of ERβcx in PC-3 cells induces GRPR mRNA expression, and GRPR immunoreactivity correlates significantly with ERβcx expression in human prostate cancer specimens. Stable transfection of ERβcx into PC-3 cells, quantitative RT-PCR, immunohistochemistry in 51 human prostate cancer specimens Neoplasma Medium 22248281
2024 IL-6 upregulates GRPR expression in hippocampal neurons, and GRP-GRPR activates the PI3K-AKT/mTOR-GSK-3β pathway. GRPR knockdown in HT22 cells abolished IL-6-induced PI3K-AKT/mTOR activation and GSK-3β upregulation. Maternal immune activation mouse model, GRPR knockdown in HT22 cells (with and without GRPR), IL-6 treatment, western blot for PI3K-AKT/mTOR/GSK-3β, NetworkAnalyst bioinformatics Journal of neuroimmune pharmacology Medium 38536552

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 211 22000021
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 166 16818949
2010 Development of a potent DOTA-conjugated bombesin antagonist for targeting GRPr-positive tumours. European journal of nuclear medicine and molecular imaging 164 20717822
2009 (68)Ga-labeled NOTA-RGD-BBN peptide for dual integrin and GRPR-targeted tumor imaging. European journal of nuclear medicine and molecular imaging 122 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 104 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
2014 Descending control of itch transmission by the serotonergic system via 5-HT1A-facilitated GRP-GRPR signaling. Neuron 95 25453842
2013 Targeting GRPR in urological cancers--from basic research to clinical application. Nature reviews. Urology 95 23507930
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
1997 Autism and multiple exostoses associated with an X;8 translocation occurring within the GRPR gene and 3' to the SDC2 gene. Human molecular genetics 88 9259269
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
2005 Species differences of bombesin analog interactions with GRP-R define the choice of animal models in the development of GRP-R-targeting drugs. Journal of nuclear medicine : official publication, Society of Nuclear Medicine 68 15872357
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 66 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 65 19910427
2016 Novel Bispecific PSMA/GRPr Targeting Radioligands with Optimized Pharmacokinetics for Improved PET Imaging of Prostate Cancer. Bioconjugate chemistry 60 26726823
2014 B-type natriuretic peptide is neither itch-specific nor functions upstream of the GRP-GRPR signaling pathway. Molecular pain 59 24438367
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
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 54 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 47 31806757
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 45 34124036
2014 PSMA, EpCAM, VEGF and GRPR as imaging targets in locally recurrent prostate cancer after radiotherapy. International journal of molecular sciences 44 24727373
2020 Peptide-Conjugated Long-Lived Theranostic Imaging for Targeting GRPr in Cancer and Immune Cells. Angewandte Chemie (International ed. in English) 42 32649787
2019 Bispecific GRPR-Antagonistic Anti-PSMA/GRPR Heterodimer for PET and SPECT Diagnostic Imaging of Prostate Cancer. Cancers 42 31540122
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 41 24508213
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 39 33789933
2019 Pain Inhibits GRPR Neurons via GABAergic Signaling in the Spinal Cord. Scientific reports 39 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
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
2008 In vitro binding evaluation of 177Lu-AMBA, a novel 177Lu-labeled GRP-R agonist for systemic radiotherapy in human tissues. Clinical & experimental metastasis 34 18975117
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
2012 Murine GRPR and stathmin control in opposite directions both cued fear extinction and neural activities of the amygdala and prefrontal cortex. PloS one 32 22312434
2023 GRP/GRPR enhances alcohol-associated liver injury through the IRF1-mediated Caspase-1 inflammasome and NOX2-dependent ROS pathway. Hepatology (Baltimore, Md.) 31 37409771
2020 Spinal GRPR and NPRA Contribute to Chronic Itch in a Murine Model of Allergic Contact Dermatitis. The Journal of investigative dermatology 31 32032577
2015 GRPR-selective PET imaging of prostate cancer using [(18)F]-lanthionine-bombesin analogs. Peptides 31 25797109
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
2016 Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer. The Prostate 30 26939805
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
2014 PESIN multimerization improves receptor avidities and in vivo tumor targeting properties to GRPR-overexpressing tumors. Bioconjugate chemistry 29 24533789
2023 Novel insight on GRP/GRPR axis in diseases. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 36933382
2022 Grpr expression defines a population of superficial dorsal horn vertical cells that have a role in both itch and pain. Pain 28 35543635
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
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
2023 GRPR-targeting radiotheranostics for breast cancer management. Frontiers in medicine 25 38020178
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
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 24 38536552
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 24 37415332
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
2023 Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy: Development of Bombesin-Based Peptide-Drug Conjugates. International journal of molecular sciences 23 36834815
1998 Human FIGF: cloning, gene structure, and mapping to chromosome Xp22.1 between the PIGA and the GRPR genes. Genomics 23 9479493
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
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 22 25474596
2016 Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer. Bioconjugate chemistry 21 27399868
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 Lower-grade gliomas surgery guided by GRPR-targeting PET/NIR dual-modality image probe: a prospective and single-arm clinical trial. Theranostics 18 38169486
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 18 38376806
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
2021 Development of Heterobivalent Theranostic Probes Having High Affinity/Selectivity for the GRPR/PSMA. Journal of medicinal chemistry 18 33534560
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
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
2021 100 Hz Electroacupuncture Alleviated Chronic Itch and GRPR Expression Through Activation of Kappa Opioid Receptors in Spinal Dorsal Horn. Frontiers in neuroscience 16 33664646
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
2024 Advances of radiolabeled GRPR ligands for PET/CT imaging of cancers. Cancer imaging : the official publication of the International Cancer Imaging Society 15 38279185
2020 GRPR-targeted SPECT imaging using a novel bombesin-based peptide for colorectal cancer detection. Biomaterials science 15 33140758
2023 GRP/GRPR signaling pathway aggravates hyperuricemia-induced renal inflammation and fibrosis via ABCG2-dependent mechanisms. Biochemical pharmacology 14 38084678
2022 Dose Rate Effects on the Selective Radiosensitization of Prostate Cells by GRPR-Targeted Gold Nanoparticles. International journal of molecular sciences 14 35563666
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
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
2021 66Ga-PET-imaging of GRPR-expression in prostate cancer: production and characterization of [66Ga]Ga-NOTA-PEG2-RM26. Scientific reports 13 33574368

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