Affinage

GALR1

Galanin receptor type 1 · UniProt P47211

Length
349 aa
Mass
39.0 kDa
Annotated
2026-06-10
71 papers in source corpus 25 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 10/10 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GALR1 is a Gi/o-coupled G protein-coupled receptor that mediates inhibitory neuromodulatory, neuroprotective, and neuroendocrine actions of the peptide galanin (PMID:9578554, PMID:12487125). The receptor binds galanin with high affinity through a hydrophobic ligand pocket formed by residues in transmembrane helices III, VI, and VII (Phe115, Glu271, Phe282) and the second extracellular loop (Phe186), with the galanin N-terminus engaging an unusually protected hydrophobic environment near TM VI (PMID:9370372, PMID:9649336, PMID:11983932). It recognizes N-terminal galanin fragments and N-terminal-directed analogues but not C-terminal fragments (PMID:8750821). Agonist binding couples exclusively to pertussis-toxin-sensitive Gi/o proteins, inhibiting basal and forskolin-stimulated adenylyl cyclase, and driving MAPK activation through a Gβγ-dependent rather than PKC-dependent route, with no Gq/phospholipase C signaling (PMID:9578554, PMID:17143559). In neurons this Gi/o/Gβγ output opens inwardly-rectifying K+ conductances to hyperpolarize cells postsynaptically and inhibits N- and P/Q-type voltage-dependent Ca2+ channels (PMID:18602374, PMID:17910903, PMID:12915763). Agonist occupancy also triggers rapid, extensive endocytosis of the ligand–receptor complex (PMID:9649336). Genetically, GALR1 mediates galanin's anticonvulsant action — knockout mice develop spontaneous seizures and suffer greater hippocampal injury in specific status epilepticus models — and contributes to neuroendocrine regulation of circulating IGF-I (PMID:12487125, PMID:15350653). GALR1 signaling is also anti-apoptotic, suppressing caspase-8 (via the inhibitor FLIP_L) and, in ischemic brain, caspase-8/-12 through downstream conventional PKCγ, conferring neuroprotection and chemoresistance (PMID:22859720, PMID:28203483). Receptor abundance is controlled transcriptionally by Scratch2 repression at an E-box in the promoter and by cAMP/CREB feedback and adrenergic crosstalk (PMID:15934937, PMID:34108238, PMID:9832123). GALR1 further assembles into heteroreceptor complexes with GalR2 and with 5-HT1A/GPR39 that allosterically rebalance signaling and shift ligand preference toward galanin(1-15) (PMID:25152404, PMID:26365466).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1995 High

    Establishing the molecular identity and pharmacology of a galanin receptor was the first requirement; cloning rat GALR1 showed it is a GPCR that binds galanin at high affinity and inhibits cAMP via a PTX-sensitive G protein.

    Evidence cDNA cloning from insulinoma cells; [125I]galanin binding and cAMP assay with pertussis toxin in heterologous cells

    PMID:8750821

    Open questions at the time
    • Did not map the ligand-binding residues
    • G-protein subtype identity inferred only from PTX sensitivity
  2. 1997 High

    Defining where galanin binds the receptor required structure-function dissection; mutagenesis identified key TM VI/VII and TM III residues that distinguish binding from functional coupling.

    Evidence Site-directed mutagenesis of hGALR1 with radioligand binding and adenylyl cyclase inhibition readouts plus N-terminally modified galanin analogues

    PMID:9370372

    Open questions at the time
    • No crystal structure to confirm pocket geometry
    • Conformational coupling between binding residues and G-protein activation unresolved
  3. 1997 High

    Genomic characterization clarified gene architecture; GALR1 has an unusual three-exon organization conserved between mouse and human.

    Evidence Genomic and cDNA cloning with Southern blotting and cross-species sequence comparison

    PMID:9271210 PMID:9367674

    Open questions at the time
    • Functional significance of the intron placements not established
    • No splice-variant function characterized
  4. 1998 High

    The G-protein selectivity and the chemical nature of the binding pocket were resolved; GALR1 couples exclusively to Gi/Gβγ, signals to MAPK independently of PKC, and binds galanin's N-terminus in a hydrophobic pocket before rapidly internalizing.

    Evidence Stable CHO/HEK lines with cAMP, GTPγS, IP, βARKct and PKC-inhibition assays; fluorescein-galanin quenching and flow-cytometry internalization assays

    PMID:9578554 PMID:9649336 PMID:9808667

    Open questions at the time
    • Endocytic machinery (arrestin/clathrin adaptors) not identified
    • Fate of internalized receptor (recycling vs degradation) unknown
  5. 2001 High

    Assigning physiological functions to receptor subtypes was needed; pharmacological dissociation showed GALR1 mediates antiallodynic effects whereas GalR2 mediates pronociception.

    Evidence Intrathecal selective agonists (AR-M1896, AR-M961) in normal and neuropathic rats with behavioral allodynia testing

    PMID:11481429

    Open questions at the time
    • Selective agonist specificity has caveats
    • Downstream spinal circuit and cell type not defined
  6. 2002 High

    Genetic loss-of-function tied GALR1 to a defined in vivo role; knockout mice develop spontaneous seizures and reduced IGF-I, establishing anticonvulsant and neuroendocrine functions.

    Evidence Galr1 knockout mice with EEG/behavioral seizure monitoring and IGF-I immunoassay; homology-modeled mutagenesis refining the pocket

    PMID:11983932 PMID:12487125

    Open questions at the time
    • Mechanism linking GALR1 to IGF-I regulation not defined
    • Anatomical locus of seizure protection not pinpointed
  7. 2004 High

    The scope of seizure protection was refined; GALR1 mediates galanin's protection in a model-specific manner, with greater injury in Li-pilocarpine and perforant path but not kainic acid models.

    Evidence GalR1 KO vs WT across three status epilepticus models with FluoroJade B/TUNEL injury scoring

    PMID:15350653

    Open questions at the time
    • Reason for model-specificity unexplained
    • Cellular substrate of hippocampal protection not isolated
  8. 2003 High

    Direct postsynaptic effector mechanisms in identified neurons were lacking; recordings showed galanin hyperpolarizes K+-channel-mediated arcuate neurons specifically in GalR1-mRNA-positive cells.

    Evidence Current-clamp recording in hypothalamic slices with post-hoc single-cell in situ hybridization and galantide antagonism

    PMID:12915763

    Open questions at the time
    • Channel identity (GIRK subtype) not molecularly confirmed
    • Signaling intermediary to the K+ channel not defined
  9. 2007 Medium

    The ionic effectors and subcellular site were extended; GALR1 opens inward-rectifier conductances postsynaptically and inhibits N-/P-Q Ca2+ channels via Gαi/Gβγ in central neurons.

    Evidence Whole-cell patch-clamp in substantia gelatinosa and NTS neurons with selective GalR1 cocktails, Gαi antibody dialysis, and prepulse protocols

    PMID:17910903 PMID:18602374

    Open questions at the time
    • Pharmacological selectivity of agonist cocktails has caveats
    • Reciprocal validation across additional neuron classes limited
  10. 2005 Medium

    Regulation of receptor abundance and the reliability of detection reagents were addressed; GALR1 expression is upregulated by cAMP/CREB activity, and brain galanin binding is essentially all GALR1 under the assayed conditions.

    Evidence Western/mRNA analysis in LC-like cells and galanin KO mice; [125I]galanin autoradiography across KO genotypes

    PMID:15708483 PMID:15934937

    Open questions at the time
    • CREB-dependence shown by correlation, direct promoter occupancy not tested here
    • Binding dominance is condition-specific
  11. 2009 High

    Interpreting prior localization data required reagent validation; available GALR1 antibodies give identical staining in KO and WT tissue, invalidating immunolocalization based on them.

    Evidence Immunohistochemistry on GalR1 KO vs WT tissue with multiple antibodies

    PMID:19159918

    Open questions at the time
    • No validated antibody offered as replacement
    • Endogenous protein distribution remains reliant on mRNA-based methods
  12. 2012 Medium

    An anti-apoptotic signaling output was defined; GALR1 silencing induces caspase-8-dependent apoptosis through loss of FLIP_L, linking the receptor to survival and chemoresistance.

    Evidence RNAi knockdown of GALR1/galanin in colorectal cancer lines with apoptosis assays, FLIP_L/caspase-8 immunoblot, and chemotherapy synergy

    PMID:22859720

    Open questions at the time
    • Signaling steps from Gi/o to FLIP_L not mapped
    • Single lab, cancer-cell context only
  13. 2014 Medium

    Receptor heteromerization as a determinant of signaling was tested; GALR1 forms GalR1–GalR2 heteromers that allosterically rebalance protomer signaling and shift potency toward galanin(1-15).

    Evidence PLA and BRET2 in HEK293T cells with CRE/NFAT luciferase reporters and selective antagonists

    PMID:25152404

    Open questions at the time
    • Heteromer existence in native tissue not demonstrated
    • Stoichiometry and interface unknown
  14. 2015 Medium

    The heteromer repertoire was broadened; GALR1 associates with GPR39 and 5-HT1A into zinc-modulated complexes with distinct signaling.

    Evidence FRET and co-immunopurification with functional signaling comparisons and zinc manipulation

    PMID:26365466

    Open questions at the time
    • Endogenous occurrence not confirmed
    • Physiological role of zinc-dependent assembly undefined
  15. 2017 Medium

    A unified neuroprotective mechanism was assembled; GALR1 mediates galanin's ischemic neuroprotection by suppressing caspase-8/-12 through downstream cPKCγ.

    Evidence MCAO model with lentiviral GalR1 RNAi, caspase activity assays, AR-M1896 comparator, and PKCγ knockout neurons

    PMID:28203483

    Open questions at the time
    • Coupling from Gi/o to cPKCγ not biochemically traced
    • Single lab
  16. 2021 Medium

    Transcriptional control of GALR1 was placed in a behavioral context; Scratch2 represses GALR1 via a promoter E-box, and its loss elevates GALR1 and produces depression-like behavior.

    Evidence Promoter luciferase reporters and Scratch2 chromatin binding plus in vivo Scratch2 knockdown with behavioral testing and RNAscope

    PMID:34108238

    Open questions at the time
    • Direct genomic occupancy in vivo not shown
    • Link between elevated GALR1 and depression phenotype is correlative
  17. 2024 Medium

    Cell-type and circuit-level functions were resolved; GALR1 marks glutamatergic neurons whose vPFC vs vHC populations differentially control attention and impulsivity.

    Evidence Multiplex FISH, GalR1-neuron-specific optogenetics, and fiber photometry during a 5-choice attention task (preprint)

    PMID:bio_10.1101_2024.07.29.605653

    Open questions at the time
    • Preprint, not peer-reviewed
    • Causal role of receptor signaling vs neuron identity not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How GALR1's Gi/o output is mechanistically routed to its caspase-suppressing/cPKCγ survival pathway and how heteromer formation is regulated in native neurons remain unresolved.
  • No biochemical chain linking Gi/o/Gβγ to FLIP_L or cPKCγ
  • No structural model of the ligand-bound receptor or heteromer interfaces
  • Endogenous heteromer occurrence and a validated detection reagent still lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3 R-HSA-5357801 Programmed Cell Death 2
Partners
GALR2GPR39HTR1A
Complex memberships
GalR1-5-HT1A-GPR39 heteroreceptor complexGalR1-GalR2 heteroreceptor complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GalR1 couples exclusively to the Gi pathway: galanin inhibits forskolin-stimulated cAMP production in GalR1/CHO cells by ~70% in a pertussis-toxin-sensitive manner, and GalR1-mediated MAPK activation is blocked by the Gβγ inhibitor βARKct but not by PKC inhibition, indicating Gi/Gβγ-dependent signaling. GalR1 does not stimulate inositol phosphate accumulation (no Gq coupling). Stable CHO cell lines expressing GalR1; cAMP assay, pertussis toxin treatment, βARKct expression, PKC inhibition/depletion, IP accumulation assay Biochemistry High 9578554
1995 Rat GALR1 is a 346-amino-acid G protein-coupled receptor that binds [125I]galanin with high affinity (two receptor states consistent with G-protein coupling), inhibits basal and forskolin-stimulated cAMP formation via a pertussis-toxin-sensitive G protein in CHO cells, and binds N-terminal galanin fragments and antagonists galantide/C7/M35/M40 but not C-terminal fragments. cDNA cloning from Rin14B insulinoma cells; [125I]galanin binding in COS1 membranes; cAMP assay in CHO cells; pertussis toxin treatment; competition binding with galanin analogues Brain research. Molecular brain research High 8750821
1997 Site-directed mutagenesis of GalR1 identified His264, Phe282, His267, Glu271, and Phe115 as key residues in the ligand-binding pocket. His264Ala and Phe282Ala mutants lose high-affinity galanin binding but remain partially functional in cAMP inhibition (~20-fold less efficient), His267Ala is also severely impaired in functional coupling (not just binding), and Glu271Lys shifts affinity toward N-terminal carboxylic acid galanin analogues, indicating that the N-terminus of galanin interacts near TM VI. Phe115Ala in TM III reduces binding affinity. Site-directed mutagenesis of hGalR1 expressed in cells; [125I]galanin competition binding; adenylyl cyclase inhibition assay; N-terminally modified galanin analogues European journal of biochemistry High 9370372
1998 Fluorescence quenching experiments with fluorescein-galanin bound to rGalR1 revealed a highly protected hydrophobic environment around the N-terminal binding region, indicating the N-terminus of galanin binds to a hydrophobic pocket within the receptor—distinct from the predominantly hydrophilic peptide–receptor interactions of other GPCRs. Agonist binding triggers rapid (t½ ~10 min), extensive (~78%) receptor-mediated internalization of the ligand–GalR1 complex via an energy-requiring endocytic process inhibited by sucrose. Fluorescein-galanin synthesis; KI fluorescence quenching assay; flow cytometry of internalization in rGalR1/CHO cells at 0°C vs 37°C; sucrose-inhibition of endocytosis Biochemistry High 9649336
2002 Molecular modelling of hGALR1 based on frog rhodopsin, combined with site-directed mutagenesis, identified Phe186 in the second extracellular loop as a hydrophobic contact residue for galanin (Phe186Ala causes 6-fold affinity decrease). Phe115Ala (TM III) reduces affinity structurally. Glu271Trp analysis suggests Glu271 interacts with the galanin N-terminus, while the corresponding Trp in GALR2 confers subtype specificity. Phe282-Tyr9(galanin) interaction is aromatic–aromatic in nature. Homology modelling (frog rhodopsin template); site-directed mutagenesis of hGALR1; radioligand binding assays with subtype-selective ligands [hGalanin(2-30), [D-Trp2]hGalanin(1-30)] Protein engineering Medium 11983932
1998 Human GALR1 stably expressed in HEK293E cells exhibits two affinity states for [125I]galanin (picomolar and nanomolar) consistent with G-protein coupling, inhibits forskolin-stimulated cAMP and stimulates GTPγS binding (full agonist profile), and the apparent antagonist M40 is actually a full agonist at GalR1 under conditions of zero receptor reserve (partial alkylation experiment), indicating that M40's in vivo antagonist effects do not arise from direct GalR1 antagonism. Stable episomal expression in HEK293E; saturation [125I]galanin binding; SPA binding assay; cAMP inhibition assay; [35S]GTPγS binding; partial alkylation (receptor inactivation) assay The Journal of pharmacology and experimental therapeutics High 9808667
2008 GalR1 activation (by GalR1-specific agonist M617 or AR-M961 in presence of GalR2 antagonist M871) in nucleus tractus solitarius neurons inhibits N- and P/Q-type voltage-dependent Ca2+ channels in a concentration-dependent manner; this inhibition is voltage-dependent (partially relieved by depolarizing prepulse) and is attenuated by intracellular Gαi antibody, identifying a Gαi/o-mediated, Gβγ-dependent suppression of VDCCs. Whole-cell patch-clamp recording in NTS neurons; selective GalR1 agonist M617; GalR1/2 agonist AR-M961; Gαi antibody dialysis; depolarizing prepulse protocol Brain research High 18602374
2007 In substantia gelatinosa neurons, GalR1 activation (AR-M961 + GalR2 antagonist M871) opens an inwardly-rectifying conductance (consistent with GIRK activation) in both excitatory and inhibitory neurons postsynaptically, whereas GalR1 agonist cocktail had no effect on spontaneous EPSCs, indicating GalR1 is not located on presynaptic terminals. Whole-cell recording from identified substantia gelatinosa neurons; pharmacological GalR1 activation cocktail (AR-M961 + M871); spontaneous EPSC analysis Pain Medium 17910903
2003 Direct patch-clamp recording of arcuate nucleus neurons in brain slices, followed by single-cell in situ hybridization, showed that galanin (500 nM) causes reversible hyperpolarization (with decreased input resistance or decreased resistance alone) via opening of K+ channels (reversal potential ~-94 mV, near EK+), blocked by galantide and by TTX-insensitive mechanism, only in neurons expressing Gal-R1 mRNA—demonstrating a direct postsynaptic inhibitory action of galanin via GalR1. Sharp microelectrode current-clamp recording in rat hypothalamic slices; biocytin labeling; post-hoc in situ hybridization for Gal-R1 mRNA on recorded neurons; galantide antagonism; TTX blockade Neuroendocrinology High 12915763
2005 GalR1 protein and mRNA levels are selectively upregulated in the locus coeruleus by increased neuronal activity or elevated cAMP (forskolin treatment), but not GalR2 or GalR3. In galanin knockout mice, reduced cAMP tone leads to increased CREB phosphorylation and elevated GalR1 expression, establishing a cAMP/CREB-dependent regulatory feedback loop for GalR1 expression. GalR1/2/3 Western blot and mRNA analysis in Cath.a cells (LC-like) with cAMP manipulations; comparison in galanin KO vs WT mouse LC; CREB phosphorylation assay Journal of neurochemistry Medium 15934937
2014 GalR1-GalR2 heteroreceptor complexes form in HEK293T cells, demonstrated by proximity ligation assay (PLA) and BRET2. Within these complexes, galanin(1-15) is more potent than galanin(1-29) in inhibiting CREB (CRE luciferase reporter) via the GalR1 protomer, while galanin(1-29) shows higher efficacy for Gq/11-mediated NFAT signaling via GalR2—indicating allosteric rebalancing of GalR1 vs GalR2 signaling when the receptors form a heteromer. PLA and BRET2 in HEK293T cells co-transfected with GalR1 and GalR2; CRE and NFAT luciferase reporter assays; selective antagonists M35 and M871 Biochemical and biophysical research communications Medium 25152404
2015 GPR39 forms heteroreceptor complexes with GalR1 (and with 5-HT1A), demonstrated by FRET and co-immunopurification; in these tripartite GalR1-5-HT1A-GPR39 heterocomplexes, downstream signaling differs from individual monomeric/homomeric receptors, and zinc modulates the formation of these specific complexes. FRET; co-immunopurification; functional signaling assays comparing monomers vs heterocomplexes; zinc manipulation Biochimica et biophysica acta Medium 26365466
2002 GALR1 knockout mice develop spontaneous tonic-clonic seizures and show reduced circulating IGF-I levels, establishing a critical role for GALR1 in mediating the anticonvulsant activity of galanin and in neuroendocrine regulation of IGF-I. Insertional inactivation of Galr1 in mice (KO); EEG/behavioral monitoring for seizures; IGF-I measurement by immunoassay; comparison to wild-type littermates Brain research. Molecular brain research High 12487125
2004 GalR1 KO mice show more severe seizures and more profound hippocampal injury (CA1, hilar interneurons, dentate granule cells) in Li-pilocarpine and perforant path stimulation models of status epilepticus, but not in kainic acid-induced seizures, indicating GalR1 mediates galanin's seizure protection in a model-specific manner. GalR1 KO vs WT mice; three SE models (Li-pilocarpine, perforant path stimulation, kainic acid); EEG seizure scoring; FluoroJade B and TUNEL for neuronal injury; BrdU for neurogenesis Neuroscience High 15350653
2001 Intrathecal low-dose galanin and GalR2-selective agonist AR-M1896 both induce mechanical and cold allodynia in normal rats, whereas intrathecal high-dose galanin or the GalR1/2 agonist AR-M961 (but not AR-M1896) reverses allodynia in neuropathic rats—establishing receptor-subtype dissociation: low-dose pronociceptive effects are GalR2-mediated, while antiallodynic effects of high-dose galanin on neuropathic pain are GalR1-mediated. Intrathecal infusion in normal and Bennett model neuropathic rats; selective GalR2 agonist AR-M1896; GalR1/2 agonist AR-M961; von Frey and cold allodynia testing Proceedings of the National Academy of Sciences of the United States of America High 11481429
2012 GalR1 silencing (RNAi) in colorectal cancer cell lines induces caspase-8-dependent apoptosis through downregulation of the caspase-8 inhibitor FLIP_L, demonstrating that GalR1/galanin signaling suppresses apoptosis via a FLIP_L-caspase-8 axis and contributes to chemotherapy resistance. RNAi knockdown of GalR1 or galanin in CRC cell lines; apoptosis assay; Western blot for FLIP_L and caspase-8; synergy with 5-FU and oxaliplatin Clinical cancer research Medium 22859720
2017 In ischemic mouse brain, GalR1 mediates the neuroprotective effect of exogenous galanin: GalR1-specific RNAi knockdown abolishes neuroprotection, and the GalR2/3 agonist AR-M1896 does not replicate it. Galanin/GalR1 inhibits caspase-8 and caspase-12 (but not caspase-9) activation to suppress apoptosis, and this protection is absent in conventional PKCγ knockout neurons, placing cPKCγ downstream of GalR1. MCAO/reperfusion mouse model; lentivirus-RNAi knockdown of GalR1; GalR2/3 agonist AR-M1896 as comparator; infarct volume; caspase activity assays (3, 8, 9, 12); PKCγ KO neurons; OGD in vitro model Aging and disease Medium 28203483
2021 The transcription factor Scratch2 binds to an E-box element in the GalR1 promoter (−250 to −220 region) to repress GalR1 transcription. Knockdown of Scratch2 in the rat ventral periaqueductal gray elevates GalR1 expression and produces depression-like behaviors; Scratch2 expression is decreased in this region in chronic mild stress rats. Luciferase reporter assay with GalR1 promoter fragments; chromatin binding by Scratch2 (molecular biology experiments in vitro); Scratch2 KD in vivo with behavioral testing; RNAscope for cell-type co-expression Proceedings of the National Academy of Sciences of the United States of America Medium 34108238
1997 GALR1 coding sequence is uniquely organized across three exons: exon 1 encodes the N-terminus through TM5, exon 2 encodes the third intracellular loop, and exon 3 encodes TM6 through the C-terminus—a gene structure conserved between mouse and human and unique among GPCRs at the time. Genomic and cDNA cloning of mouse GalR1; Southern blotting; sequencing; comparison with human GALNR gene structure FEBS letters High 9271210 9367674
1998 GALR1 mRNA and protein are co-expressed with galanin in human ocular ciliary epithelium (NPE/PE cells and ODM-2 cell line); alpha2-adrenergic receptor activation upregulates GalR-1 receptor mRNA (4–5-fold) while beta2-adrenergic activation downregulates galanin mRNA, identifying adrenergic receptor crosstalk as a regulatory mechanism for GalR1 expression in ciliary epithelial cells. RT-PCR; Northern blot; alpha2- and beta2-adrenergic agonist/antagonist pharmacology; quantitative mRNA analysis in ODM-2 cells; radioimmunoassay for galanin peptide Journal of neurochemistry Medium 9832123
2005 Under the experimental conditions used (autoradiography), essentially all specific [125I]-galanin binding in mouse brain is abolished in GalR1 KO mice, indicating that under these conditions galanin binding is attributable predominantly to GalR1 with negligible contribution from other subtypes. [125I]-galanin autoradiography in brain sections of WT, galanin KO, and GalR1 KO mice on two genetic backgrounds Neuroscience Medium 15708483
2024 Multiplex FISH in rat brain established that GalR1 is predominantly expressed in glutamatergic (not GABAergic) neurons in both the ventral PFC and ventral hippocampus. Optogenetic excitation of GalR1-expressing neurons in the vPFC (but not vHC) selectively disrupted visuospatial attention in the 5-choice task. Fiber photometry revealed opposing activity patterns: GalR1-expressing vPFC neurons increase activity during correct attentive actions, while vHC GalR1-expressing neurons signal impulsive errors. Multiplex fluorescent in situ hybridization (RNAscope); novel viral approach for GalR1-neuron-specific optogenetics; 5-choice serial reaction time task; fiber photometry calcium imaging bioRxivpreprint Medium bio_10.1101_2024.07.29.605653
2007 GAL-R1 and GAL-R2 (but not GAL-R3) mRNAs are expressed in dispersed rat adrenocortical cells, and galanin stimulates corticosterone and cAMP release through both receptor subtypes coupled to the adenylate cyclase/PKA pathway; phospholipase C inhibition and PKC inhibition have no effect, establishing that GalR1 in adrenocortical cells signals exclusively through cAMP/PKA and not through the Gq/PLC pathway. RT-PCR; [3H]galanin binding with subtype-specific antibody immunoblockade; corticosterone and cAMP radioimmunoassay; PKA inhibitor H-89; adenylyl cyclase inhibitor SQ-22536; PLC inhibitor U-73122; PKC inhibitor calphostin-C International journal of molecular medicine Medium 17143559
2009 Commercially and academically available antibodies to GalR1 produce identical immunoreactivity patterns in wild-type and GalR1 knockout mouse tissues, indicating these antibodies do not specifically detect endogenous GalR1 under standard immunodetection conditions—a negative finding that invalidates prior immunolocalization data obtained with these reagents. Immunohistochemistry/immunofluorescence on tissues from GalR1 KO and WT mice using multiple GalR1 antibodies Naunyn-Schmiedeberg's archives of pharmacology High 19159918

Source papers

Stage 0 corpus · 71 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
1995 Cloning and characterization of the rat GALR1 galanin receptor from Rin14B insulinoma cells. Brain research. Molecular brain research 196 8750821
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
2003 Galanin GAL-R1 receptor null mutant mice display increased anxiety-like behavior specific to the elevated plus-maze. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 161 12700679
2004 Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GalR1) knockout mice. Neuroscience 80 15350653
2002 Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity. Brain research. Molecular brain research 77 12487125
2004 Learning and memory performance in mice lacking the GAL-R1 subtype of galanin receptor. The European journal of neuroscience 66 15016096
1997 Semiquantitative distribution of galanin-receptor (GAL-R1) mRNA-containing cells in the male rat hypothalamus. Neuroendocrinology 65 9380273
1997 Genomic organization and functional characterization of the mouse GalR1 galanin receptor. FEBS letters 64 9271210
2004 Characterization of GalR1, GalR2, and GalR3 immunoreactivity in catecholaminergic nuclei of the mouse brain. The Journal of comparative neurology 61 15514977
2003 Galanin acts at GalR1 receptors in spinal antinociception: synergy with morphine and AP-5. The Journal of pharmacology and experimental therapeutics 58 14610237
2009 Analyzing the validity of GalR1 and GalR2 antibodies using knockout mice. Naunyn-Schmiedeberg's archives of pharmacology 57 19159918
2012 Identification of galanin and its receptor GalR1 as novel determinants of resistance to chemotherapy and potential biomarkers in colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 51 22859720
1999 Evidence for expression of galanin receptor Gal-R1 mRNA in certain gonadotropin releasing hormone neurones of the rostral preoptic area. Journal of neuroendocrinology 50 10520130
2003 Altered hippocampal expression of neuropeptides in seizure-prone GALR1 knockout mice. Epilepsia 47 12887433
2005 Galanin impairs performance on learning and memory tasks: findings from galanin transgenic and GAL-R1 knockout mice. Neuropeptides 37 15944016
1997 Pharmacological characterization and tissue distribution of the human and rat GALR1 receptors. Biochemical and biophysical research communications 37 9168941
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
2015 The zinc binding receptor GPR39 interacts with 5-HT1A and GalR1 to form dynamic heteroreceptor complexes with signaling diversity. Biochimica et biophysica acta 33 26365466
2000 Upregulation of galanin binding sites and GalR1 mRNA levels in the mouse locus coeruleus following chronic morphine treatments and precipitated morphine withdrawal. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 33 10882839
1998 Evidence for hydrophobic interaction between galanin and the GalR1 galanin receptor and GalR1-mediated ligand internalization: fluorescent probing with a fluorescein-galanin. Biochemistry 33 9649336
1998 Effects of estrous cyclicity on the expression of the galanin receptor Gal-R1 in the rat preoptic area: a comparison with the male. Endocrinology 31 9751492
1997 Structural organization of the mouse and human GALR1 galanin receptor genes (Galnr and GALNR) and chromosomal localization of the mouse gene. Genomics 31 9367674
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
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
2002 Molecular modelling and site-directed mutagenesis of human GALR1 galanin receptor defines determinants of receptor subtype specificity. Protein engineering 28 11983932
1997 Mutagenesis and ligand modification studies on galanin binding to its GTP-binding-protein-coupled receptor GalR1. European journal of biochemistry 27 9370372
2011 The neuropeptide galanin and variants in the GalR1 gene are associated with nicotine dependence. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 26 21796100
2005 [125I]-Galanin binding in brain of wildtype, and galanin- and GalR1-knockout mice: strain and species differences in GalR1 density and distribution. Neuroscience 26 15708483
1997 GALR1 galanin receptor mRNA is co-expressed by galanin neurons but not cholinergic neurons in the rat basal forebrain. Brain research. Molecular brain research 25 9450684
2012 Pharmacogenetic association of the galanin receptor (GALR1) SNP rs2717162 with smoking cessation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 24 22373943
2013 GALR1 methylation in vaginal swabs is highly accurate in identifying women with endometrial cancer. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 23 23727823
2015 Epigenetic inactivation of galanin and GALR1/2 is associated with early recurrence in head and neck cancer. Clinical & experimental metastasis 22 26572146
2005 Human galanin (GAL) and galanin 1 receptor (GALR1) variations are not involved in fat intake and early onset obesity. The Journal of nutrition 22 15930442
2023 Alleviation of Limosilactobacillus reuteri in polycystic ovary syndrome protects against circadian dysrhythmia-induced dyslipidemia via capric acid and GALR1 signaling. NPJ biofilms and microbiomes 20 37422471
2018 Inhibition of GALR1 in PFC Alleviates Depressive-Like Behaviors in Postpartum Depression Rat Model by Upregulating CREB-BNDF and 5-HT Levels. Frontiers in psychiatry 20 30487761
2005 Increased hyperalgesia after tissue injury and faster recovery of allodynia after nerve injury in the GalR1 knockout mice. Neuropeptides 20 15944015
1998 Pharmacological and biochemical characterization of a recombinant human galanin GALR1 receptor: agonist character of chimeric galanin peptides. The Journal of pharmacology and experimental therapeutics 19 9808667
2017 Galanin Protects from Caspase-8/12-initiated Neuronal Apoptosis in the Ischemic Mouse Brain via GalR1. Aging and disease 18 28203483
2003 Direct inhibitory action of galanin on hypothalamic arcuate nucleus neurones expressing galanin receptor Gal-r1 mRNA. Neuroendocrinology 17 12915763
2018 Galanin/GalR1-3 system: A promising therapeutic target for myocardial ischemia/reperfusion injury. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 30551408
1998 Molecular identification and coexpression of galanin and GalR-1 galanin receptor in the human ocular ciliary epithelium: differential modulation of their expression by the activation of alpha2- and beta2-adrenergic receptors in cultured ciliary epithelial cells. Journal of neurochemistry 16 9832123
2014 Central injection of GalR1 agonist M617 facilitates GLUT4 expression in cardiac muscle of type 2 diabetic rats. Experimental gerontology 14 25449850
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
2008 Variation in Galr1 expression determines susceptibility to exocitotoxin-induced cell death in mice. Genes, brain, and behavior 13 18363852
2004 Regulation of galanin receptor GalR1 mRNA expression by ovarian steroids in oestrogen receptor alpha-immunoreactive neurones: identification of distinct populations of neurones in the preoptic area. Journal of neuroendocrinology 13 14764000
2008 Galanin inhibits calcium channels via Galpha(i)-protein mediated by GalR1 in rat nucleus tractus solitarius. Brain research 12 18602374
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
1998 Mutagenesis study on human galanin receptor GalR1 reveals domains involved in ligand binding. Annals of the New York Academy of Sciences 11 9928161
2021 Cell-type specific expression and behavioral impact of galanin and GalR1 in the locus coeruleus during opioid withdrawal. Addiction biology 10 33768673
2016 Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway. Mechanisms of ageing and development 10 27041232
2005 Induction of galanin receptor-1 (GalR1) expression in external granule cell layer of post-natal mouse cerebellum. Journal of neurochemistry 10 15748163
2002 Expression of galanin receptor-1 (GALR1) in the rat trigeminal ganglia and molar teeth. Neuroscience research 10 11900829
2010 Characterization of the chicken galanin type I receptor (GalR1) and a novel GalR1-like receptor (GalR1-L). General and comparative endocrinology 8 20977910
2021 Involvement of Scratch2 in GalR1-mediated depression-like behaviors in the rat ventral periaqueductal gray. Proceedings of the National Academy of Sciences of the United States of America 6 34108238
2012 Galanin, through GalR1 but not GalR2 receptors, decreases motivation at times of high appetitive behavior. Behavioural brain research 6 23142608
2015 A Pyrosequencing Assay for the Quantitative Methylation Analysis of GALR1 in Endometrial Samples: Preliminary Results. BioMed research international 5 26504828
2022 Promoter hypermethylation of GALR1 acts as an early epigenetic susceptibility event in colorectal carcinogenesis. Journal of human genetics 4 35606503
2020 Association Between Polymorphisms in the 5' Region of the GALR1 Gene and Schizophrenia in the Northern Chinese Han Population: A Case-Control Study. Neuropsychiatric disease and treatment 4 32606704
1998 Retrovirus-mediated expression of the GalR1 galanin receptor: implication for efficient stable expression of functional G protein-coupled receptors. Journal of receptor and signal transduction research 4 9879063
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
2025 GALR1 and PENK serve as potential biomarkers in invasive non-functional pituitary neuroendocrine tumours. Gene 2 40024300
2021 Time-restricted feeding prevents metabolic diseases through the regulation of galanin/GALR1 expression in the hypothalamus of mice. Eating and weight disorders : EWD 1 34370270
2026 Intravenous galanin (1-16) and a GalR1 agonist attenuate allodynia in rats with spared nerve injury. Pain reports 0 41822106
2025 The potential neuro-oncology link of GALR1 protein molecular mechanism in breast cancer: Expression in BT549 and MDA-MB-231 cells and its role in proliferation and migration. International journal of biological macromolecules 0 40032112

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