Affinage

GALR2

Galanin receptor type 2 · UniProt O43603

Length
387 aa
Mass
41.7 kDa
Annotated
2026-06-10
67 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALR2 is a galanin-activated G-protein-coupled receptor that couples primarily to Gq/G11 to stimulate phospholipase C, inositol phosphate production, and intracellular calcium mobilization, while also engaging Gi/o to modestly inhibit forskolin-stimulated cAMP (PMID:9578554, PMID:9685625, PMID:9832121). Its MAPK activation is PKC-dependent and insensitive to Gβγ inhibition, distinguishing it mechanistically from GalR1, which signals through a Giβγ pathway (PMID:9578554). The receptor binds galanin with subnanomolar affinity and, unlike GalR1/GalR3, tolerates N-terminal extension and C-terminal deletion of the peptide (PMID:9480833); high-affinity galanin binding and downstream IP signaling depend cooperatively on membrane cholesterol (PMID:10508403). Through these signaling outputs GALR2 drives diverse cell- and tissue-level programs: it is required for galanin-stimulated neurite outgrowth from sensory neurons via a PKC-dependent pathway (PMID:12533601), mediates hippocampal neuroprotection through Akt and ERK (PMID:17263796), and promotes neurogenesis of hippocampal precursors (PMID:21281311). Depending on cellular context the same receptor can trigger caspase-dependent apoptosis associated with downregulation of pAkt/pBad in neuronal cell models (PMID:14592962, PMID:18272487). GALR2 transduces pronociceptive spinal effects and modulates neuronal excitability both pre- and postsynaptically (PMID:11481429, PMID:17910903), mediates jejunal and uterine smooth muscle contractility (PMID:9742938, PMID:34203944), and protects the heart and astrocytes against oxidative and ischemia/reperfusion injury (PMID:35431947, PMID:37249014, PMID:31249471). In disease contexts it promotes tumor angiogenesis in head and neck squamous cell carcinoma via RAP1B/p38-mediated inactivation of tristetraprolin and consequent VEGF/IL-6 secretion (PMID:24568968), and drives epithelial-to-mesenchymal transition and perineural invasion in salivary adenoid cystic carcinoma (PMID:36039037). GALR2 forms GalR1-GalR2 heteroreceptor complexes with altered ligand pharmacology and biased signaling (PMID:25152404), and can engage β-arrestin2-biased signaling — independent of Gq — to exert anti-inflammatory protection of the gut epithelium (PMID:41390752). The receptor is pharmacologically tractable to positive allosteric modulation at a site distinct from the orthosteric galanin pocket (PMID:20660766).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Established that GALR2 is a galanin receptor distinct from GalR1 in its G-protein coupling, defining the molecular basis for divergent galaninergic signaling.

    Evidence cAMP, inositol phosphate, calcium and MAPK assays with PTX, PKC inhibitor and beta-ARKct dissection in CHO/COS-7/HEK-293 stable and transient lines, plus radioligand binding and melanophore/aequorin readouts across human, rat and mouse orthologs

    PMID:9480833 PMID:9578554 PMID:9685625 PMID:9832121 PMID:9832122

    Open questions at the time
    • Stoichiometry and selectivity of Gq versus Gi/o engagement in native neurons not resolved
    • No structural basis for the differential ligand tolerance versus GalR1/GalR3
  2. 1998 Medium

    Assigned GALR2 to specific physiological functions by tissue-level pharmacology, showing it mediates jejunal contraction and is upregulated after motor nerve injury but does not drive galanin's orexigenic effect.

    Evidence Rat jejunal organ-bath contractility with GalR-selective ligands plus RT-PCR; in situ hybridization in a facial nerve crush model

    PMID:9681481 PMID:9742938

    Open questions at the time
    • Autoreceptor role inferred from mRNA upregulation without functional confirmation
    • Downstream effectors of contractile and injury responses not defined
  3. 1999 High

    Identified membrane cholesterol as a required cofactor for high-affinity galanin binding and signaling, revealing a lipid-dependent regulatory layer on GALR2 function.

    Evidence Methyl-beta-cyclodextrin cholesterol depletion/re-addition with radioligand binding and IP accumulation, controlled for membrane fluidity and G-protein interaction in CHO/GalR2 cells

    PMID:10508403

    Open questions at the time
    • Cholesterol-binding residues/sites on the receptor not mapped
    • Physiological relevance in native tissues untested
  4. 2001 High

    Defined the in vivo spinal role of GALR2 as pronociceptive, separating it from the antiallodynic GalR1-mediated effect of galanin.

    Evidence Intrathecal GalR2-selective agonist AR-M1896 versus GalR1/2 agonist in a rat neuropathic pain model with behavioral allodynia endpoints

    PMID:11481429

    Open questions at the time
    • Intracellular signaling underlying pronociception not identified
    • Cellular site (neuronal subtype) of action not defined
  5. 2003 High

    Demonstrated that GALR2 governs opposing cell-fate outcomes — neurite outgrowth versus apoptosis — depending on cellular context, both downstream of Gq/PKC signaling.

    Evidence DRG cultures from galanin-KO/GalR1-KO/WT mice with receptor-selective agonist and PKC inhibitor for neuritogenesis; tetracycline-inducible GalR2 in SH-SY5Y with caspase-3, PARP and DNA laddering for apoptosis

    PMID:12533601 PMID:14592962

    Open questions at the time
    • Molecular switch determining trophic versus apoptotic outcome unknown
    • Apoptosis demonstrated in transfected/overexpression contexts
  6. 2007 High

    Mapped the neuroprotective signaling of GALR2 to Akt and ERK pathways and detailed its electrophysiological actions on spinal neurons.

    Evidence GalR2 loss-of-function mutant hippocampal cultures with pAkt/pERK Westerns and kinase inhibitors under glutamate challenge; whole-cell patch-clamp of substantia gelatinosa neurons with subtype-selective tools

    PMID:17263796 PMID:17910903

    Open questions at the time
    • Link between Gq coupling and Akt activation not mechanistically resolved
    • In vivo contribution of presynaptic versus postsynaptic actions not separated
  7. 2008 High

    Connected GALR2-induced apoptosis to suppression of the PI3K/Akt/Bad survival axis, contrasting with cell-cycle arrest in cells lacking the receptor.

    Evidence Stable GFP-GalR2 PC12 cells with caspase, pAkt/pBad/p21 Westerns, PI3K inhibitor and FACS cell-cycle analysis versus non-transfected controls

    PMID:18272487

    Open questions at the time
    • Reconciliation with neuroprotective Akt activation in other models unresolved
    • Dependence on overexpression context
  8. 2010 High

    Showed GALR2 is amenable to positive allosteric modulation, establishing a non-orthosteric pharmacological handle on the receptor.

    Evidence CYM2503 potentiation of galanin-stimulated IP1 in HEK293/GalR2 with no orthosteric binding, plus an in vivo seizure model

    PMID:20660766

    Open questions at the time
    • Allosteric binding site not structurally defined experimentally
    • Effect on Gi/o and arrestin pathways untested
  9. 2014 High

    Defined a GALR2 oncogenic signaling pathway in head and neck cancer and characterized GalR1-GalR2 heteromers as functionally biased signaling units.

    Evidence SCCHN cell lines with GALR2 overexpression, TTP/RAP1B knockdown, p38 inhibitors and multiple xenograft models; PLA/BRET2 and CRE/NFAT reporters for heteromer pharmacology in HEK293T

    PMID:24568968 PMID:25152404

    Open questions at the time
    • Heteromer detection from a single lab without reciprocal validation
    • Generality of the RAP1B-p38-TTP axis to other GALR2 functions unknown
  10. 2019 Medium

    Extended GALR2 cytoprotective signaling to astrocytes against oxidative stress through modulation of ERK.

    Evidence Rat cortical astrocyte H2O2 model with GalR2 agonist AR-M1896 and pERK1/2 Westerns

    PMID:31249471

    Open questions at the time
    • Agonist mimicry without genetic loss-of-function validation
    • Direction of ERK modulation differs from neuronal neuroprotection model
  11. 2021 Medium

    Implicated GALR2 in metabolic regulation by linking it to a GLUT4/insulin-sensitizing signaling axis in skeletal muscle.

    Evidence Obese mouse model and L6 myotubes with GALR2 siRNA and antagonist M871, measuring glucose consumption and PGC-1alpha/GLUT4/p-p38/p-AKT/p-AS160

    PMID:34923235

    Open questions at the time
    • Direct receptor-to-GLUT4 mechanism not established
    • Single lab, pharmacological agent (baicalin) driven
  12. 2022 Medium

    Established GALR2 as the dominant cardiac galanin receptor with a protective role against hypertrophy, fibrosis and mitochondrial oxidative stress, and as a driver of EMT-mediated perineural invasion in salivary carcinoma.

    Evidence In vivo GalR2 suppression and H9C2 siRNA with histology and mitochondrial ROS; SACC-neuron co-culture with transcriptomics, EMT Westerns, invasion assays and M871 antagonism in vivo

    PMID:35431947 PMID:36039037

    Open questions at the time
    • Cardiac protective signaling pathway downstream of GalR2 not fully defined
    • Both findings from single labs
  13. 2023 Medium

    Confirmed GALR2 as the principal mediator of galanin cardioprotection in acute ischemia/reperfusion injury.

    Evidence Rat LAD occlusion/reperfusion with GalR2-selective agonist G1 and M871 antagonist, measuring infarct size and CK-MB

    PMID:37249014

    Open questions at the time
    • Intracellular cardioprotective signaling not delineated
    • Single lab pharmacological study
  14. 2025 High

    Revealed that GALR2 can signal through beta-arrestin2 independently of Gq to exert anti-inflammatory, gut-barrier-protective effects, establishing biased agonism as a physiologically relevant GALR2 output.

    Evidence DSS colitis in chickens and mice with Galr2-KO, epithelial-specific Arrb2-KO and Gnaq-KO defining the pathway by epistasis

    PMID:41390752

    Open questions at the time
    • Ligand/structural determinants of arrestin bias not defined
    • Relationship between arrestin-biased and Gq-mediated GALR2 functions unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • An experimentally validated structural model of GALR2 ligand and allosteric binding sites, and a unifying account of how one receptor selects among Gq, Gi/o and beta-arrestin2 outputs to produce opposing cell fates, remain unresolved.
  • Binding-site residues predicted only by homology modeling, without mutagenesis or experimental structure (idx 26)
  • No mechanism explaining context-dependent choice between trophic, apoptotic and anti-inflammatory signaling

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0048018 receptor ligand activity 2 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-112316 Neuronal System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
GALGALR1
Complex memberships
GalR1-GalR2 heteroreceptor complex

Evidence

Reading pass · 27 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 increase inositol phosphate (IP) production (7-fold in CHO/COS-7 cells), and also couples modestly to Gi to inhibit forskolin-stimulated cAMP. GALR2-mediated MAPK activation is abolished by PKC inhibition but not by beta-ARKct (Gbetagamma inhibitor), consistent with Go-mediated MAPK activation, distinct from GalR1 which uses a Gibetagamma pathway. CHO and COS-7 cell lines stably/transiently expressing GalR1 or GalR2; cAMP assay, inositol phosphate accumulation assay, MAPK activation 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 forskolin-stimulated cAMP accumulation, as demonstrated in HEK-293 cells stably expressing human GALR2. HEK-293 stable cell lines; radioligand binding ([125I]porcine galanin), cAMP assay, calcium measurement, Xenopus melanophore pigment aggregation assay, aequorin luminescence Brain research. Molecular brain research High 9685625
1998 Human GALR2 binds galanin with high affinity (Kd ~0.24–0.3 nM). The receptor tolerates N-terminal extension and C-terminal deletion of galanin (unlike GalR1/GalR3) and uses phosphatidylinositol hydrolysis and calcium mobilization as its primary signaling mechanism. COS-7 transient transfection; [125I]galanin radioligand binding (saturation, displacement), calcium mobilization assay, RT-PCR tissue distribution Biochemical and biophysical research communications Medium 9480833
1998 Human GALR2 and GALR3 were cloned; human GALR2 binds galanin with high affinity (Kd = 0.3 nM) and signals through phospholipase C/intracellular calcium elevation (Gq/11), in contrast to GALR1 and GALR3 which signal predominantly through inhibition of adenylate cyclase. GALR2 gene is on chromosome 17q25. HEK-293 cell expression; [125I]galanin radioligand binding, aequorin luminescence (intracellular calcium), Xenopus melanophore assay, FISH chromosomal localization Journal of neurochemistry High 9832121
1998 Mouse GALR2 encodes a 370-aa GPCR with high homology to rat GalR2 (94%), binds [125I]galanin with high affinity (Kd = 0.47 nM), and stimulates phosphoinositide metabolism upon galanin activation in a pertussis-toxin-insensitive manner, confirming Gq rather than Gi coupling. COS-7 transient transfection; radioligand binding, displacement assay with galanin analogs, phosphoinositide metabolism assay, pertussis toxin treatment Journal of neurochemistry High 9832122
1998 GALR2 mRNA is upregulated ~3.7-fold in ipsilateral facial nucleus 7 days after facial nerve crush, while GalR1 mRNA was not detected in facial nuclei, suggesting a specific autoreceptor-like role for GalR2 in motor neuron injury response. In situ hybridization histochemistry in rat facial nerve crush model; time-course analysis Journal of neurochemistry Medium 9681481
1998 GalR2 agonist activity and pharmacological profile in the rat jejunum matches the GalR2 subtype (high GalR2 mRNA detected there), identifying GalR2 as the receptor mediating jejunal contraction. GalR2-selective ligands did not reproduce the feeding behavior, excluding GalR2 from mediating galanin's orexigenic effect. Rat jejunal contraction assay with GalR-selective ligands, RT-PCR for receptor mRNA expression in tissue, feeding behavior assay FEBS letters Medium 9742938
1999 Membrane cholesterol is required for galanin binding to GalR2; cholesterol depletion markedly reduces galanin binding, which is restored by cholesterol re-addition. GalR2 binds multiple cholesterol molecules cooperatively (Hill n ≥ 3). This effect is independent of membrane fluidity and G protein interaction, and cholesterol depletion also impairs GalR2-mediated IP accumulation. Methyl-beta-cyclodextrin cholesterol depletion, cholesterol re-addition, radioligand binding assays, IP accumulation assay, GTP-gamma-S treatment in CHO/GalR2 cells Biochemistry High 10508403
2001 Intrathecal infusion of a GalR2-specific agonist (AR-M1896) induces mechanical and cold allodynia at low doses in normal rats, demonstrating a pronociceptive role for spinal GalR2. By contrast, the antiallodynic effect of high-dose galanin in neuropathic (Bennett model) rats is mediated by GalR1, not GalR2. Rat neuropathic pain model (Bennett); intrathecal infusion of GalR2-specific agonist AR-M1896 vs. GalR1/2 agonist AR-M961; behavioral allodynia testing Proceedings of the National Academy of Sciences of the United States of America High 11481429
2003 GalR2 activation is required for galanin-stimulated neurite outgrowth from adult DRG sensory neurons. A GalR2-specific agonist had equipotent effects to galanin on neuritogenesis, GalR1 knockout or antagonism had no effect, and inhibition of PKC reduced outgrowth to galanin-KO levels, placing GalR2 upstream of a PKC-dependent neuritogenic pathway. DRG neuronal cultures from galanin-KO, GalR1-KO, and WT mice; galanin peptide rescue, GalR1-specific antagonist, GalR2-specific agonist, PKC inhibitor; neurite outgrowth quantification The Journal of neuroscience High 12533601
2003 GalR2 activation induces apoptosis in SH-SY5Y neuroblastoma cells; tetracycline-induced GalR2 expression followed by galanin treatment caused 93% decrease in cell viability, caspase-3 activation, PARP cleavage, and DNA laddering. GalR1 activation caused only 19% reduction with no apoptotic morphology. Tetracycline-controlled expression system in SH-SY5Y cells; microphysiometry, viability assay, PARP cleavage, caspase-3 activation, DNA laddering Endocrinology High 14592962
2007 GalR2 activation mediates galanin's neuroprotective effect in hippocampal neurons. In GalR2 loss-of-function mutant hippocampal cultures, galanin-induced phosphorylation of Akt (435% in WT) was markedly attenuated and the protective effect of galanin was abolished. GalR2 activates both Akt and ERK signaling pathways; specific inhibition of either pathway confirmed their contribution to neuroprotection. GalR2 loss-of-function mutant mouse hippocampal cultures, galanin-KO cultures, galanin-overexpressing cultures; Western blot for pAkt and pERK, specific kinase inhibitors, glutamate challenge Journal of neurochemistry High 17263796
2007 GalR2 activation in substantia gelatinosa neurons decreases membrane excitability (measured by action potential latency) and inhibits presynaptic glutamate release (increased EPSC interevent interval), while GalR1 activation activates an inwardly-rectifying conductance. GalR2 was confirmed to act both postsynaptically and presynaptically. Whole-cell patch-clamp recording from rat substantia gelatinosa neurons; selective GalR1 'cocktail' (AR-M961 + M871 antagonist) vs. GalR2-selective agonist AR-M1896; current-voltage analysis, spontaneous EPSC recording Pain High 17910903
2008 GalR2 activation by galanin or GalR2/3-agonist AR-M1896 induces caspase-dependent apoptotic cell death in GalR2-transfected PC12 cells, associated with downregulation of pAkt and pBad (Gq/11 pathway downstream). PI3K inhibitor LY-294002 increased pBad and reduced caspase activation. Non-transfected PC12 cells showed only cell cycle arrest (upregulation of p21cip1) without apoptosis. Stable GFP-GalR2-transfected PC12 cells; cell viability, caspase assay, Western blot (pAkt, pBad, p21cip1), PI3K inhibitor, FACS cell cycle analysis, real-time PCR Proceedings of the National Academy of Sciences of the United States of America High 18272487
2010 CYM2503 acts as a positive allosteric modulator (PAM) of GalR2: it potentiated galanin-stimulated IP1 accumulation in HEK293/GalR2 cells but showed no detectable affinity for the [125I]galanin orthosteric binding site, demonstrating allosteric modulation of GalR2 is pharmacologically achievable. HEK293 stable GalR2 cells; IP1 accumulation assay, [125I]galanin radioligand binding competition assay; in vivo Li-pilocarpine seizure model Proceedings of the National Academy of Sciences of the United States of America High 20660766
2014 GALR2 promotes tumor angiogenesis in head and neck squamous cell carcinoma (SCCHN) via p38-MAPK-mediated secretion of VEGF and IL-6. The mechanism involves GALR2 activation of RAP1B, leading to p38-mediated inactivation (phosphorylation) of tristetraprolin (TTP), a cytokine mRNA destabilizing protein, resulting in enhanced cytokine secretion. SCCHN cell lines with GALR2 overexpression; ELISA (VEGF, IL-6), in vitro angiogenesis assay, chemical p38 inhibitors, genetic knockdown of TTP/RAP1B, mouse xenograft, chick CAM, orthotopic floor-of-mouth models Molecular cancer therapeutics High 24568968
2014 GalR1 and GalR2 form heteroreceptor complexes (GalR1-GalR2 heteromers) detectable by proximity ligation assay (PLA) and BRET2 in HEK293T cells and in the raphe-hippocampal system. Within these complexes, galanin(1-15) is more potent than galanin(1-29) in inhibiting CREB (via GalR1 protomer/Gi), while galanin(1-29) has higher efficacy for Gq/11-mediated NFAT signaling (via GalR2 protomer), demonstrating biased signaling in the heteromer context. HEK293T transfection; proximity ligation assay (PLA), BRET2, CRE luciferase reporter assay, NFAT reporter assay, M35 (non-selective) and M871 (GalR2-selective) antagonists Biochemical and biophysical research communications Medium 25152404
2021 Baicalin reduces insulin resistance in skeletal muscle via activation of the GALR2/GLUT4 signaling pathway, elevating PGC-1α, GLUT4, p-p38MAPK, p-AKT, and p-AS160. These effects were abolished by GALR2 antagonist M871 in vivo and by GALR2 knockdown or M871 in L6 myotubes in vitro. Obese mouse model; L6 myotube GALR2 siRNA knockdown; GALR2 antagonist M871; glucose consumption, Western blot (PGC-1α, GLUT4, p-p38MAPK, p-AKT, p-AS160) Phytomedicine Medium 34923235
2022 GalR2 is the dominant galanin receptor subtype in adult mouse hearts and cardiomyocytes. Genetic suppression of GalR2 in vivo promotes cardiac hypertrophy, fibrosis, and mitochondrial oxidative stress. In vitro, GalR2 siRNA knockdown abolished the beneficial effects of galanin on cardiomyocyte hypertrophy and mitochondrial ROS production. Adult mouse heart/cardiomyocyte expression profiling; in vivo GalR2 genetic suppression; siRNA knockdown in H9C2 cardiomyoblasts; cardiac hypertrophy/fibrosis histology, mitochondrial ROS measurement Frontiers in pharmacology Medium 35431947
2022 Nerve-derived galanin activates GALR2 on salivary adenoid cystic carcinoma (SACC) cells to induce epithelial-to-mesenchymal transition (EMT), enhancing proliferation, migration, invasion, and perineural invasion. These effects were blocked by the GALR2-specific antagonist M871 both in vitro and in vivo. Co-culture of SACC cells with DRG/SH-SY5Y neurons; transcriptome sequencing, Western blot (EMT markers), Transwell invasion/migration, in vitro and in vivo PNI models, M871 GALR2 antagonist Cancer medicine Medium 36039037
2023 GalR2 is the principal receptor subtype transducing cardioprotective effects of galanin and GalR2-specific agonist G1 in rat myocardial ischemia/reperfusion (I/R) injury. Intravenous G1 reduced infarct size by 35% and CK-MB activity by 43%; these effects were abolished by co-administration of the selective GalR2 antagonist M871. Rat in vivo LAD coronary artery occlusion/reperfusion model; GalR2-specific agonist G1 vs. full-length galanin G2; M871 antagonist; infarct size measurement, plasma CK-MB activity Fundamental & clinical pharmacology Medium 37249014
2019 GalR2 mediates galanin's protective effect on rat cortical astrocytes against oxidative stress. GalR2 is expressed at higher levels than GalR1 or GalR3 in cultured cortical astrocytes. GalR2 agonist AR-M1896 mimicked galanin's protection. Galanin suppressed H2O2-induced upregulation of pERK1/2 in astrocytes. Cultured rat cortical astrocytes; H2O2 oxidative stress model; receptor subtype expression (GalR1/2/3), GalR2 agonist AR-M1896, Western blot for pERK1/2, cell viability assay Mediators of inflammation Medium 31249471
2025 cGAL53 (a chicken long galanin isoform) protects the gut barrier and reduces colitis-associated inflammation via β-arrestin2-biased GALR2 signaling. Effects were abolished in Galr2-deficient mice and in epithelial cell-specific Arrb2 knockout mice, demonstrating that GALR2 anti-inflammatory signaling proceeds through β-arrestin2 rather than Gq. DSS-induced colitis in chickens and mice; Galr2 knockout mice, epithelial cell-specific Arrb2 and Gnaq knockout mice; inflammatory markers, gut barrier assays Nature communications High 41390752
2011 GalR2/3 activation (using Gal2-11 agonist) is both trophic and proliferative for postnatal hippocampal subgranular zone precursors and neuroblasts; GalR1 activation had no effect on neurogenesis. Postnatal hippocampal precursor cultures; GalR2/3 agonist Gal2-11 vs. GalR1-selective ligands; proliferation and trophic assays Journal of neurochemistry Medium 21281311
2007 GAL-R2, but not GAL-R3, participates in galanin-mediated inhibition of uterine contractile amplitude and frequency, as demonstrated by reversal of galanin effects with GALR2 antagonist. Inflammation reduced GALR1 protein expression in pig myometrium, altering the balance of receptor contributions. Ex vivo pig uterine contractility assay; E. coli-induced endometritis model; GALR2 antagonist, GALR1/GALR2 combined antagonist; Western blot for GALR1 International journal of molecular sciences Medium 34203944
2007 In rat adrenocortical cells, GAL-R1 and GAL-R2 (but not GAL-R3) mediate galanin-stimulated corticosterone and cAMP release via an adenylate cyclase/PKA-dependent pathway. Inositol triphosphate production was not affected. Immuno-blockade of both GAL-R1 and GAL-R2 was required for complete inhibition of galanin binding. Dispersed rat inner adrenocortical cells; RT-PCR, [3H]galanin binding, receptor immuno-blockade, corticosterone/cAMP/IP3 assays, adenylate cyclase inhibitor SQ-22536, PKA inhibitor H-89, PLC inhibitor U-73122, PKC inhibitor calphostin-C International journal of molecular medicine Medium 17143559
2016 Homology modeling and molecular dynamics simulation identified residues Tyr160(4.60), Ile105(3.32), Ala274(7.35), and Tyr163(ECL2) as important for galanin binding to GALR2. The putative allosteric binding pocket (pocket III) for PAMs is formed by galanin, ECL2, TM2, TM3, and ECL1; PAM binding at this site disrupts the Na+-binding site/pathway, promoting receptor agonism. Homology modeling, molecular docking, 50-ns molecular dynamics simulation; model validated against known experimental binding data Journal of molecular modeling Low 27021209

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 182 11481429
1998 Molecular characterization and expression of cloned human galanin receptors GALR2 and GALR3. Journal of neurochemistry 149 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 61 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 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 45 9742938
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 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
2021 Baicalin protects against insulin resistance and metabolic dysfunction through activation of GALR2/GLUT4 signaling. Phytomedicine : international journal of phytotherapy and phytopharmacology 32 34923235
2011 GalR2/3 mediates proliferative and trophic effects of galanin on postnatal hippocampal precursors. Journal of neurochemistry 32 21281311
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 25 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
2023 GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions. Journal of cellular physiology 18 36599082
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
2017 Preclinical evaluation of intravenous NAX 810-2, a novel GalR2-preferring analog, for anticonvulsant efficacy and pharmacokinetics. Epilepsia 17 28098336
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 14 18595677
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
2022 Galanin Receptors (GALR1, GALR2, and GALR3) Immunoexpression in Enteric Plexuses of Colorectal Cancer Patients: Correlation with the Clinico-Pathological Parameters. Biomolecules 13 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 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 11 35346778
2022 Galanin Regulates Myocardial Mitochondrial ROS Homeostasis and Hypertrophic Remodeling Through GalR2. Frontiers in pharmacology 11 35431947
2021 Regulatory Influence of Galanin and GALR1/GALR2 Receptors on Inflamed Uterus Contractility in Pigs. International journal of molecular sciences 11 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 11 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 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 7 38549164
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
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 6 38572811
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 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
2022 Investigating the potential of GalR2 as a drug target for neuropathic pain. Neuropeptides 4 36580831
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
1999 Characterization of hypothalamic neurons expressing a neuropeptide receptor, GALR2, using combined in situ hybridization-immunohistochemistry. Methods (San Diego, Calif.) 3 10491278
2025 Intracerebroventricular knockdown of NPY1R disrupts NPY1R-GALR2/TrkB heteroreceptor complexes without affecting neuroplasticity or depressive-like behaviour. Journal of psychopharmacology (Oxford, England) 1 41307298
2025 A novel long-galanin peptide from non-mammalian vertebrates mitigates the inflammatory response in IBD models via the biased GALR2/β-arrestin2 pathway. Nature communications 1 41390752
2026 The role of galanin/GALR2 signaling in the link between type 2 diabetes and Alzheimer's disease. Neuropeptides 0 41570651
2022 [The anti-ischemic and antioxidant activity of the pharmacological agonist of galanin receptor GalR2 and carnosine in in vitro and in vivo model systems]. Biomeditsinskaia khimiia 0 35717583

Missed literature

Know a paper Affinage missed for GALR2? Flag it for the maintainers and the community.

No submissions yet.