Affinage

GALR2

Galanin receptor type 2 · UniProt O43603

Length
387 aa
Mass
41.7 kDa
Annotated
2026-04-28
67 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALR2 is a galanin receptor that functions as a Gq/G11-coupled GPCR activating phospholipase C, inositol phosphate production, and intracellular calcium mobilization, with secondary coupling to Gi/Go-mediated cAMP inhibition and a recently established beta-arrestin2-biased signaling arm (PMID:9578554, PMID:9685625, PMID:41390752). Downstream of Gq, GALR2 engages PKC-dependent MAPK activation, Akt/ERK-mediated neuroprotection in hippocampal neurons, and PKC-dependent neurite outgrowth from sensory neurons, while also triggering caspase-3-dependent apoptosis through Akt/Bad downregulation in neuroblastoma and PC12 cells (PMID:12533601, PMID:17263796, PMID:14592962, PMID:18272487). Ligand binding requires membrane cholesterol, which cooperatively modulates both receptor affinity and Gq-dependent signaling independently of G protein coupling (PMID:10508403). GALR2 forms heteroreceptor complexes with GalR1 that allosterically reshape ligand selectivity between Gi and Gq pathways, and in peripheral tissues drives tumor angiogenesis via RAP1B/p38/TTP-dependent stabilization of VEGF and IL-6 mRNAs and protects the gut epithelium through beta-arrestin2-biased anti-inflammatory signaling (PMID:25152404, PMID:24568968, PMID:41390752).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1998 High

    Establishing the primary signaling identity of GALR2: multiple groups independently demonstrated that GALR2 couples predominantly to Gq/G11 to activate PLC and inositol phosphate/calcium signaling, with modest Gi/Go-mediated cAMP inhibition and PKC-dependent MAPK activation, distinguishing it mechanistically from GalR1 and GalR3.

    Evidence Heterologous expression in CHO, HEK-293, COS-7, and Xenopus melanophore systems with cAMP, inositol phosphate, calcium, and MAPK assays plus pertussis toxin and PKC inhibitor dissection

    PMID:9578554 PMID:9685625 PMID:9832121 PMID:9832122

    Open questions at the time
    • Endogenous G-protein stoichiometry may differ from overexpression systems
    • Structural basis for preferential Gq over Gi coupling unknown
  2. 1998 Medium

    Identifying GALR2 as the functional galanin receptor subtype in smooth muscle contraction resolved which receptor mediates galanin's gut motility effects, linking GALR2 Gq signaling to a defined physiological output.

    Evidence Pharmacological profiling with GalR-selective ligands in rat jejunal contraction assay combined with Northern blot/RT-PCR

    PMID:9742938

    Open questions at the time
    • Genetic confirmation with GALR2 knockout in gut tissue not performed
    • Downstream contractile signaling pathway not dissected
  3. 1999 High

    Demonstrating that membrane cholesterol is an obligate modulator of GALR2 ligand binding and downstream Gq signaling revealed a lipid-dependent regulatory layer operating independently of G-protein coupling.

    Evidence Cholesterol depletion/repletion in CHO/GalR2 cells with radioligand binding, Hill analysis, and inositol phosphate assays

    PMID:10508403

    Open questions at the time
    • Direct cholesterol binding site on GALR2 not identified
    • No structural data for cholesterol-receptor interaction
  4. 2001 High

    Establishing GALR2 as a pronociceptive receptor in the spinal cord — where low-dose galanin induces allodynia via GALR2 while high-dose antiallodynia is GalR1-mediated — resolved a long-standing paradox of galanin's bidirectional effects on pain.

    Evidence Intrathecal infusion of GalR2-selective agonist AR-M1896 in rat neuropathic pain model with mechanical and cold allodynia testing

    PMID:11481429

    Open questions at the time
    • Downstream intracellular pathway linking GALR2 activation to allodynia not identified
    • GALR2 knockout confirmation not performed
  5. 2003 High

    Two independent studies established GALR2 as an effector of both neurite outgrowth (via PKC) in sensory neurons and caspase-3-dependent apoptosis in neuroblastoma cells, revealing divergent cell-type-dependent outcomes of the same Gq/PKC pathway.

    Evidence GalR1 knockout mice plus selective agonist/antagonist pharmacology in DRG neurite outgrowth assay; inducible GalR2 expression in SH-SY5Y with caspase-3, PARP cleavage, and DNA laddering assays

    PMID:12533601 PMID:14592962

    Open questions at the time
    • Branching point determining growth versus death outcome not identified
    • Role of Gi coupling in apoptosis not excluded
  6. 2007 High

    Genetic loss-of-function in mice demonstrated that GALR2 is required for galanin-induced Akt and ERK phosphorylation in hippocampal neurons and for protection against glutamate excitotoxicity, establishing GALR2 as a neuroprotective receptor.

    Evidence GalR2 loss-of-function mutant mice, hippocampal cultures, Western blot for pAkt/pERK, kinase inhibitors

    PMID:17263796

    Open questions at the time
    • Nature of the GalR2 loss-of-function allele limits generalizability
    • Relative contribution of Akt versus ERK arm not fully resolved
  7. 2007 High

    Electrophysiological recordings established that GALR2 acts presynaptically in spinal substantia gelatinosa neurons to decrease excitability and modulate excitatory synaptic transmission, providing a synaptic-level mechanism for galanin's sensory modulatory effects.

    Evidence Whole-cell patch-clamp with GalR2-selective agonist AR-M1896 and antagonist M871 in rat substantia gelatinosa neurons

    PMID:17910903

    Open questions at the time
    • Ion channel target downstream of presynaptic GALR2 not identified
    • Post-synaptic GalR2 contributions not fully dissected
  8. 2008 High

    Mechanistic dissection in PC12 cells revealed that GALR2-induced apoptosis proceeds via Gq-coupled downregulation of pAkt and pBad, placing Bad dephosphorylation as the specific pro-apoptotic switch downstream of GALR2.

    Evidence Stable GFP-GalR2 PC12 cells, Western blot for pAkt/pBad, caspase assay, PI3K inhibitor LY-294002

    PMID:18272487

    Open questions at the time
    • How Gq activation leads to Akt downregulation (rather than activation as in hippocampus) remains unexplained
    • Cell-type determinants of pro-survival versus pro-apoptotic outcome unknown
  9. 2010 High

    Discovery of CYM2503 as a positive allosteric modulator of GALR2 demonstrated that GALR2 Gq signaling can be potentiated without competing at the orthosteric galanin binding site, opening a new pharmacological modality with in vivo anticonvulsant efficacy.

    Evidence IP1 accumulation assay and radioligand binding in HEK293/GalR2 cells; rat Li-pilocarpine and mouse electroshock seizure models

    PMID:20660766

    Open questions at the time
    • Allosteric binding site on GALR2 not mapped
    • Selectivity over GalR1/GalR3 in vivo not fully characterized
  10. 2014 High

    Two parallel advances: (1) GalR1-GalR2 heteroreceptor complexes were shown to allosterically shape galanin fragment selectivity between Gi and Gq outputs; (2) GALR2 was found to drive tumor angiogenesis through p38/RAP1B-mediated TTP inactivation and VEGF/IL-6 mRNA stabilization.

    Evidence BRET2 and PLA in HEK293T cells with CRE/NFAT reporters for heteromers; ELISA, in vitro angiogenesis, genetic knockdown of RAP1B/TTP, mouse xenograft and CAM models for angiogenesis

    PMID:24568968 PMID:25152404

    Open questions at the time
    • Stoichiometry and structural architecture of GalR1-GalR2 heteromer unknown
    • Whether TTP-dependent mechanism operates in cancers beyond HNSCC not tested
  11. 2022 Medium

    Loss-of-function studies in cardiomyocytes and cardiac tissue established GALR2 as a cardioprotective receptor whose suppression promotes hypertrophy, fibrosis, and mitochondrial oxidative stress, extending GALR2 biology beyond the nervous system.

    Evidence GalR2 genetic suppression in mice and siRNA in H9C2 cardiomyoblasts with cardiac histology and mitochondrial ROS measurement; validated with selective agonist/antagonist in ischemia-reperfusion model

    PMID:35431947 PMID:37249014

    Open questions at the time
    • Downstream signaling pathway (Gq versus Gi versus biased) mediating cardioprotection not dissected
    • Single-lab findings await independent replication
  12. 2025 High

    Conditional knockout studies revealed that GALR2 can signal through beta-arrestin2 independently of canonical Gq coupling to protect the gut epithelial barrier and suppress colitis, establishing biased agonism as a physiologically relevant GALR2 signaling mode.

    Evidence Galr2 knockout, epithelial cell-specific Arrb2 and Gnaq conditional knockout mice in DSS-induced colitis model with colon histology and inflammatory markers

    PMID:41390752

    Open questions at the time
    • Whether beta-arrestin2 bias is ligand-dependent (cGAL53-specific) or generalizable to all GALR2 agonists unknown
    • Structural basis for biased signaling at GALR2 not determined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the structural basis for GALR2's preferential Gq coupling, cholesterol binding, and allosteric modulation; the cell-type determinants that switch GALR2 output between pro-survival (Akt/ERK) and pro-apoptotic (Akt/Bad) fates; and whether beta-arrestin2-biased signaling operates in neuronal and cardiac contexts.
  • No high-resolution structure of GALR2 available
  • Cell-type switching mechanism between neuroprotection and apoptosis undefined
  • Beta-arrestin2 bias characterized only in gut epithelium

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-5357801 Programmed Cell Death 2
Partners
ARRB2GALR1GNAIGNAQRAP1BZFP36
Complex memberships
GalR1-GalR2 heteroreceptor complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GalR2 couples to Gq/G11 to stimulate phospholipase C and inositol phosphate production (7-fold increase), and also couples modestly to Gi (30% inhibition of forskolin-stimulated cAMP) and Go-mediated MAPK activation in CHO cells; GalR2-mediated MAPK activation is PKC-dependent and not sensitive to beta-ARKct (Gbetagamma inhibitor), distinguishing it mechanistically from GalR1. Stable CHO cell expression, cAMP assay, inositol phosphate accumulation, MAPK activity assay, pertussis toxin treatment, PKC inhibitor, beta-ARKct expression Biochemistry High 9578554
1998 Human GALR2 couples to Galphaq/11 to stimulate phospholipase C and increase intracellular calcium, and also to Galphai/o to inhibit adenylate cyclase; high-affinity galanin binding (Kd ~0.3 nM) requires intact N-terminal but not C-terminal galanin fragments. Stable HEK-293 expression, [125I]galanin radioligand binding, cAMP assay, calcium/aequorin luminescence, Xenopus melanophore assay Brain research. Molecular brain research High 9685625
1998 Human GALR2 couples to phospholipase C/calcium mobilization, distinguishing it from GALR1 and GALR3 which signal predominantly through inhibition of adenylate cyclase; galanin binds with Kd ~0.3 nM. Radioligand binding ([125I]galanin), aequorin luminescence calcium assay, Xenopus melanophore assay in HEK-293 cells Journal of neurochemistry High 9832121
1998 Mouse GalR2 signals through phosphoinositide metabolism (Gq-coupled) in a pertussis toxin-insensitive manner, confirming Gq (not Gi/Go) as the primary coupling partner; high-affinity galanin binding (Kd = 0.47 nM) requires N-terminal but not C-terminal galanin sequences. COS-7 cell transfection, [125I]galanin radioligand binding, phosphoinositide metabolism assay, pertussis toxin treatment Journal of neurochemistry High 9832122
1999 Membrane cholesterol is required for galanin binding to GalR2; depletion by methyl-beta-cyclodextrin or lipoprotein-deficient serum markedly reduces binding, which is restored by cholesterol repletion. GalR2 binds multiple cholesterol molecules cooperatively (Hill n ≥ 3). Cholesterol also modulates downstream Gq/inositol phosphate signaling, independently of G protein interaction. Cholesterol depletion/repletion in CHO/GalR2 cells, radioligand binding, Hill analysis, filipin clustering, cholesterol oxidase treatment, inositol phosphate assay, GTPgammaS preincubation Biochemistry High 10508403
1998 GalR2 is the receptor subtype mediating galanin-induced jejunal contraction; pharmacological profile of GalR-selective ligands in jejunal contraction matched only GalR2, and only GalR2 mRNA was detected in the tissue. GalR-selective ligand pharmacology in rat jejunal contraction assay, Northern blot/RT-PCR for receptor mRNA FEBS letters Medium 9742938
1998 GalR2 mRNA is markedly upregulated (~3.7-fold at day 7) in facial motor neurons after unilateral facial nerve crush, while GalR1 mRNA is absent in facial nuclei; this inducible GalR2 upregulation suggests an autoreceptor role in nerve injury response. In situ hybridization histochemistry quantification after facial nerve crush in rats Journal of neurochemistry Medium 9681481
2001 GalR2 receptor activation mediates pronociceptive (allodynic) effects of low-dose galanin in the spinal cord; intrathecal infusion of the GalR2-specific agonist AR-M1896 induces mechanical and cold allodynia in normal rats, whereas antiallodynic effects of high-dose galanin in neuropathic pain are mediated by GalR1. Intrathecal infusion of GalR2-selective agonist AR-M1896 and GalR1/2 agonist AR-M961 in rat Bennett neuropathic pain model, mechanical and cold allodynia testing Proceedings of the National Academy of Sciences of the United States of America High 11481429
2003 GalR2 activation mediates galanin-induced neurite outgrowth from adult dorsal root ganglion sensory neurons via a PKC-dependent signaling pathway; GalR2-specific agonist has equipotent effects to galanin on neurite extension, PKC inhibition reduces outgrowth to galanin-knockout levels, and GalR1 knockout/antagonism has no effect. GalR1 knockout animals, GalR1-specific antagonist, GalR2-specific agonist, PKC inhibitor, DRG neurite outgrowth assay, galanin knockout cultures The Journal of neuroscience High 12533601
2003 GalR2 activation in SH-SY5Y neuroblastoma cells induces apoptosis via caspase-3 activation, PARP cleavage, and DNA laddering; this effect is far more potent (100-fold lower EC50) and pronounced than GalR1 activation in the same cell type. Tetracycline-inducible GalR1/GalR2 expression in SH-SY5Y cells, cell viability, caspase-3 activation, PARP cleavage, DNA laddering, microphysiometry Endocrinology High 14592962
2007 GalR2 mediates neuroprotection in hippocampal neurons by activating Akt and ERK phosphorylation; galanin-induced Akt phosphorylation is abolished in GalR2 loss-of-function mutant animals. Inhibitors of ERK or Akt confirm that GalR2-dependent activation of these kinases contributes to protection against glutamate-induced cell death. GalR2 loss-of-function mutant mice, hippocampal cultures, galanin/glutamate treatment, Western blot for pAkt and pERK, specific kinase inhibitors Journal of neurochemistry High 17263796
2007 GalR2 is expressed presynaptically in substantia gelatinosa neurons, where its activation by selective agonist AR-M1896 consistently decreases membrane excitability and increases the interevent interval of spontaneous EPSCs; GalR1 cocktail does not affect EPSCs, demonstrating distinct pre- versus postsynaptic localization. Whole-cell patch-clamp recording from rat substantia gelatinosa neurons, GalR2-selective agonist AR-M1896, GalR2 antagonist M871, current-voltage analysis, EPSC recording Pain High 17910903
2008 GalR2 activation in PC12 cells stably expressing GFP-tagged GalR2 induces caspase-dependent apoptosis via Gq/11-type signaling, associated with downregulation of pAkt and pBad; PI3K inhibition increases pBad and decreases caspase activation, confirming PI3K/Akt pathway involvement downstream of GalR2. Stable GFP-GalR2 transfection in PC12 cells, Western blot for pAkt/pBad, caspase activation assay, PI3K inhibitor LY-294002, FACS cell cycle analysis, real-time PCR Proceedings of the National Academy of Sciences of the United States of America High 18272487
2010 CYM2503, a positive allosteric modulator of GalR2, potentiates galanin-stimulated IP1 accumulation in HEK293/GalR2 cells without displacing [125I]galanin from the orthosteric binding site, demonstrating allosteric modulation of GalR2 Gq signaling; this compound shows anticonvulsant efficacy in rodent seizure models. IP1 accumulation assay in HEK293/GalR2 cells, [125I]galanin radioligand binding competition, rat Li-pilocarpine seizure model, mouse electroshock model Proceedings of the National Academy of Sciences of the United States of America High 20660766
2014 GalR1 and GalR2 form heteroreceptor complexes detectable by proximity ligation assay (PLA) and BRET2 in HEK293T cells and in the raphe-hippocampal system; within these complexes, galanin(1-15) preferentially activates the GalR1 protomer (inhibiting CREB/cAMP via Gi) while galanin(1-29) shows higher efficacy at the GalR2 protomer (activating Gq/NFAT signaling), revealing allosteric receptor-receptor interactions. Proximity ligation assay, BRET2 assay in HEK293T cells, CRE luciferase reporter, NFAT luciferase reporter, GalR2 antagonist M871, galanin antagonist M35 Biochemical and biophysical research communications High 25152404
2014 GALR2 promotes tumor angiogenesis in head and neck squamous cell carcinoma via p38-MAPK-mediated activation of RAP1B, which phosphorylates/inactivates tristetraprolin (TTP), stabilizing VEGF and IL-6 mRNA transcripts and enhancing their secretion; p38 inhibition reactivates TTP and decreases cytokine secretion. ELISA for cytokines, in vitro angiogenesis assay, p38 chemical inhibitor, genetic knockdown of RAP1B and TTP, mouse xenograft, chick chorioallantoic membrane, orthotopic floor-of-mouth model Molecular cancer therapeutics High 24568968
2021 GALR2 activation by baicalin upregulates GLUT4 expression and glucose uptake through p38MAPK and AKT pathways and the PGC-1alpha-GLUT4 axis in skeletal muscle; GALR2 antagonist M871 and GALR2 siRNA knockdown abolish these effects, demonstrating that GALR2 is the required mediator. Obese mouse model with GALR2 antagonist M871, GALR2 knockdown L6 myotubes, Western blot for PGC-1alpha/GLUT4/p-p38/p-AKT/p-AS160, glucose consumption assay Phytomedicine Medium 34923235
2022 GalR2 is the dominant galanin receptor subtype in mouse cardiomyocytes and hearts; genetic suppression of GalR2 promotes cardiac hypertrophy, fibrosis, and mitochondrial oxidative stress in vivo, while GalR2 siRNA in vitro abolishes galanin's protective effects against cell hypertrophy and mitochondrial ROS production. GalR2 genetic suppression in mice, siRNA knockdown in H9C2 cardiomyoblasts, cardiac histology, mitochondrial ROS measurement Frontiers in pharmacology Medium 35431947
2022 Nerve-derived galanin activates GALR2 in salivary adenoid cystic carcinoma cells, inducing epithelial-to-mesenchymal transition (EMT) and promoting perineural invasion; GALR2 antagonist M871 blocks these effects both in vitro and in vivo. Transcriptome sequencing, Western blot for EMT markers, Transwell invasion assay, in vitro and in vivo perineural invasion models, GALR2 antagonist M871 Cancer medicine Medium 36039037
2023 GalR2 is the principal receptor subtype transducing cardioprotective effects of galanin in myocardial ischemia/reperfusion injury; the GalR2-selective agonist peptide G1 (1 mg/kg i.v.) reduced infarct size by 35% and CK-MB activity by 43%, and these effects were abolished by the selective GalR2 antagonist M871. LAD coronary artery occlusion/reperfusion in rats, GalR2-selective agonist and antagonist (M871), infarct size measurement, plasma CK-MB activity Fundamental & clinical pharmacology Medium 37249014
2025 GALR2 mediates the anti-inflammatory effects of a naturally occurring long galanin isoform (cGAL53) via beta-arrestin2-biased signaling rather than canonical Gq; these effects were abolished in Galr2-deficient mice and in epithelial cell-specific Arrb2 knockout mice, demonstrating that GALR2/beta-arrestin2 pathway protects the gut barrier and reduces colitis-associated inflammation. Galr2 knockout mice, epithelial cell-specific Arrb2 and Gnaq conditional knockouts, DSS-induced colitis model, colon histology, inflammatory markers Nature communications High 41390752
2007 GAL-R2, expressed in rat adrenocortical cells, couples to the adenylate cyclase/PKA signaling cascade to stimulate corticosterone secretion; immunoblockade of GAL-R2 (and GAL-R1) reduced galanin binding and abolished cAMP and corticosterone responses, while PLC inhibitor and PKC inhibitor had no effect. Dispersed rat adrenocortical cells, immunoblockade of receptor subtypes, [3H]galanin binding, cAMP and inositol phosphate assays, adenylate cyclase inhibitor SQ-22536, PKA inhibitor H-89, PKC inhibitor International journal of molecular medicine Medium 17143559
2011 GalR2/3 activation by Gal2-11 promotes proliferation and trophic survival of postnatal hippocampal subgranular zone precursors and neuroblasts; no effect was observed via GalR1, demonstrating receptor-subtype specificity for hippocampal neurogenesis. Postnatal hippocampal precursor culture, GalR2/3 agonist Gal2-11, proliferation and survival assays Journal of neurochemistry Medium 21281311
2019 GalR2 mediates galanin's protective effects against oxidative stress in rat cortical astrocytes; GalR2 agonist AR-M1896 mimics galanin protection against H2O2 toxicity and suppresses H2O2-induced upregulation of pERK1/2, with GalR2 showing higher expression than GalR1 or GalR3 in these cells. Primary rat cortical astrocyte culture, H2O2 oxidative stress, GalR2-selective agonist AR-M1896, Western blot for pERK1/2, cell viability assay Mediators of inflammation Medium 31249471

Source papers

Stage 0 corpus · 67 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1. The Journal of comparative neurology 282 10379831
1998 Differential intracellular signaling of the GalR1 and GalR2 galanin receptor subtypes. Biochemistry 212 9578554
2001 Receptor subtype-specific pronociceptive and analgesic actions of galanin in the spinal cord: selective actions via GalR1 and GalR2 receptors. Proceedings of the National Academy of Sciences of the United States of America 181 11481429
1998 Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. Journal of neurochemistry 148 9832121
2003 The second galanin receptor GalR2 plays a key role in neurite outgrowth from adult sensory neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 117 12533601
2007 Activation of the galanin receptor 2 (GalR2) protects the hippocampus from neuronal damage. Journal of neurochemistry 94 17263796
2007 Galanin receptor subtype 2 (GalR2) null mutant mice display an anxiogenic-like phenotype specific to the elevated plus-maze. Pharmacology, biochemistry, and behavior 92 17257664
1999 Membrane cholesterol modulates galanin-GalR2 interaction. Biochemistry 85 10508403
2005 Phenotypic analysis of mice deficient in the type 2 galanin receptor (GALR2). Molecular and cellular biology 67 15899880
2003 Galanin receptor subtype GalR2 mediates apoptosis in SH-SY5Y neuroblastoma cells. Endocrinology 67 14592962
1998 Molecular characterization, pharmacological properties and chromosomal localization of the human GALR2 galanin receptor. Brain research. Molecular brain research 66 9685625
2008 Phenotypic analysis of GalR2 knockout mice in anxiety- and depression-related behavioral tests. Neuropeptides 64 18554714
2004 Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain. The Journal of comparative neurology 60 15514977
1999 Expression of the galanin receptor subtype Gal-R2 mRNA in the rat hypothalamus. Journal of chemical neuroanatomy 59 10450874
2009 Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice. Naunyn-Schmiedeberg's archives of pharmacology 57 19159918
1998 Cloning and expression of the human galanin receptor GalR2. Biochemical and biophysical research communications 53 9480833
1998 Distribution and characterization of the cell types expressing GALR2 mRNA in brain and pituitary gland. Annals of the New York Academy of Sciences 45 9928165
1998 The GalR2 galanin receptor mediates galanin-induced jejunal contraction, but not feeding behavior, in the rat: differentiation of central and peripheral effects of receptor subtype activation. FEBS letters 44 9742938
1998 Inducible galanin and GalR2 receptor system in motor neuron injury and regeneration. Journal of neurochemistry 43 9681481
1998 Cloning and characterization of the human galanin GALR2 receptor. Peptides 41 9880084
2009 A novel GalR2-specific peptide agonist. Neuropeptides 39 19467704
2008 Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2). Proceedings of the National Academy of Sciences of the United States of America 38 18272487
2008 The effects of galanin-like peptide on energy balance, body temperature and brain activity in the mouse and rat are independent of the GALR2/3 receptor. Journal of neuroendocrinology 37 18081561
2014 Preferential activation by galanin 1-15 fragment of the GalR1 protomer of a GalR1-GalR2 heteroreceptor complex. Biochemical and biophysical research communications 36 25152404
2000 Expression of GalR1 and GalR2 galanin receptor messenger ribonucleic acid in proopiomelanocortin neurons of the rat arcuate nucleus: effect of testosterone. Endocrinology 36 10803589
2010 Engineering galanin analogues that discriminate between GalR1 and GalR2 receptor subtypes and exhibit anticonvulsant activity following systemic delivery. Journal of medicinal chemistry 35 20121116
1998 The mouse GalR2 galanin receptor: genomic organization, cDNA cloning, and functional characterization. Journal of neurochemistry 33 9832122
2011 GalR2/3 mediates proliferative and trophic effects of galanin on postnatal hippocampal precursors. Journal of neurochemistry 32 21281311
2021 Baicalin protects against insulin resistance and metabolic dysfunction through activation of GALR2/GLUT4 signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 31 34923235
2005 GalR1, but not GalR2 or GalR3, levels are regulated by galanin signaling in the locus coeruleus through a cyclic AMP-dependent mechanism. Journal of neurochemistry 29 15934937
2014 The G protein-coupled receptor GALR2 promotes angiogenesis in head and neck cancer. Molecular cancer therapeutics 28 24568968
2007 Selective stimulation of GalR1 and GalR2 in rat substantia gelatinosa reveals a cellular basis for the anti- and pro-nociceptive actions of galanin. Pain 28 17910903
2010 GalR2-positive allosteric modulator exhibits anticonvulsant effects in animal models. Proceedings of the National Academy of Sciences of the United States of America 27 20660766
2020 Palmitate differentially regulates Spexin, and its receptors Galr2 and Galr3, in GnRH neurons through mechanisms involving PKC, MAPKs, and TLR4. Molecular and cellular endocrinology 24 32841709
2006 Galanin treatment offsets the inhibition of bone formation and downregulates the increase in mouse calvarial expression of TNFalpha and GalR2 mRNA induced by chronic daily injections of an injurious vehicle. Bone 21 17157570
2014 Analgesic properties of a peripherally acting and GalR2 receptor-preferring galanin analog in inflammatory, neuropathic, and acute pain models. The Journal of pharmacology and experimental therapeutics 19 25347995
1998 Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin receptor, in the control of pain perception. Annals of the New York Academy of Sciences 18 9928164
2023 GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions. Journal of cellular physiology 17 36599082
2017 Preclinical evaluation of intravenous NAX 810-2, a novel GalR2-preferring analog, for anticonvulsant efficacy and pharmacokinetics. Epilepsia 17 28098336
2007 Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade. International journal of molecular medicine 14 17143559
2008 Immunohistochemical localization of galanin receptors (GAL-R1, GAL-R2, and GAL-R3) on myenteric neurons from the sheep and dog stomach. Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft 13 18595677
2022 Galanin Receptors (GALR1, GALR2, and GALR3) Immunoexpression in Enteric Plexuses of Colorectal Cancer Patients: Correlation with the Clinico-Pathological Parameters. Biomolecules 12 36551197
2012 Identification and characterization of the chicken galanin receptor GalR2 and a novel GalR2-like receptor (GalR2-L). General and comparative endocrinology 12 22982974
2023 Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 11 36848750
2022 Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2. Frontiers in pharmacology 11 35431947
2022 Effects of intracerebroventricular injection of spexin and its interaction with NPY, GalR2 and GalR3 receptors on the central food intake regulation and nutritional behavior in broiler chickens. Neuroscience letters 10 35346778
2021 Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs. International journal of molecular sciences 10 34203944
2016 The Influence of Gastric Antral Ulcerations on the Expression of Galanin and GalR1, GalR2, GalR3 Receptors in the Pylorus with Regard to Gastric Intrinsic Innervation of the Pyloric Sphincter. PloS one 10 27175780
2022 The GAL/GALR2 axis promotes the perineural invasion of salivary adenoid cystic carcinoma via epithelial-to-mesenchymal transition. Cancer medicine 9 36039037
2017 Preclinical Analgesic and Safety Evaluation of the GalR2-preferring Analog, NAX 810-2. Neurochemical research 9 28382595
2016 Homology modeling, docking, and molecular dynamics simulation of the receptor GALR2 and its interactions with galanin and a positive allosteric modulator. Journal of molecular modeling 8 27021209
2024 Neuropeptide Y receptor 1 and galanin receptor 2 (NPY1R-GALR2) interactions in the dentate gyrus and their relevance for neurogenesis and cognition. Frontiers in cellular neuroscience 6 38425430
2022 Chimeric Agonist of Galanin Receptor GALR2 Reduces Heart Damage in Rats with Streptozotocin-Induced Diabetes. Biochemistry. Biokhimiia 6 35527373
2022 Levels of spexin and its receptors GALR2 and GALR3 in the hypothalamus and ovary of letrozole-induced polycystic ovary syndrome in rats. Biochemical and biophysical research communications 6 36055012
2019 Galanin Protects Rat Cortical Astrocyte from Oxidative Stress: Involvement of GalR2 and pERK1/2 Signal Pathway. Mediators of inflammation 6 31249471
2012 Galanin, through GalR1 but not GalR2 receptors, decreases motivation at times of high appetitive behavior. Behavioural brain research 6 23142608
2024 Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions. Behavioral and brain functions : BBF 5 38549164
2024 Long-term enhancements in antidepressant efficacy and neurogenesis: Effects of intranasal co-administration of neuropeptide Y 1 receptor (NPY1R) and galanin receptor 2 (GALR2) agonists in the ventral hippocampus. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 38572811
2024 Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for major depressive disorder. Expert opinion on therapeutic targets 5 38622072
2024 Glyphosate-induced changes in the expression of galanin and GALR1, GALR2 and GALR3 receptors in the porcine small intestine wall. Scientific reports 3 38632282
2023 Exogenous GalR2-specific peptide agonist as a tool for treating myocardial ischemia/reperfusion injury. Fundamental & clinical pharmacology 3 37249014
2022 Investigating the potential of GalR2 as a drug target for neuropathic pain. Neuropeptides 3 36580831
1999 Characterization of hypothalamic neurons expressing a neuropeptide receptor, GALR2, using combined in situ hybridization-immunohistochemistry. Methods (San Diego, Calif.) 3 10491278
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