Affinage

NPY

Pro-neuropeptide Y · UniProt P01303

Round 2 corrected
Length
97 aa
Mass
10.9 kDa
Annotated
2026-04-29
130 papers in source corpus 37 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPY is a 36-amino acid neuropeptide processed from a 97-amino acid precursor (preproNPY) that functions as a co-transmitter with noradrenaline in sympathetic neurons and as a major hypothalamic regulator of energy homeostasis, neuroendocrine function, and stress-related behavior (PMID:6589611, PMID:2858824, PMID:2170253). NPY signals through Gi-coupled Y1, Y2, Y4, and Y5 receptors with subtype-specific binding poses — cryo-EM structures reveal that the NPY N-terminus engages Y1 but not Y2/Y4 — and couples to inhibition of cAMP and elevation of intracellular Ca²⁺ in a cell-type-dependent manner (PMID:1321422, PMID:7592910, PMID:35507650). In the hypothalamus, NPY neurons integrate excitatory ghrelin input (via PKA/N-type Ca²⁺ channels and a UCP2-dependent mitochondrial fatty acid oxidation pathway) and inhibitory leptin input to drive feeding primarily through Y1 receptors — as established by Y1-knockout mice showing dramatically reduced NPY-induced food intake — while Y5 receptors mediate reductions in energy expenditure and suppression of LH secretion (PMID:18668043, PMID:11737554, PMID:10698177, PMID:10465275, PMID:12697685). Beyond energy balance, NPY exerts Y1-mediated antidepressant-like and anxiolytic effects, promotes adult neurogenesis via Y1/ERK1/2 signaling, provides Y2 receptor-dependent neuroprotection against excitotoxicity, suppresses POMC-to-α-MSH processing through Y1/Egr-1-mediated downregulation of PC2, and modulates ethanol consumption as demonstrated by reciprocal knockout and overexpression models (PMID:11927186, PMID:21175616, PMID:18412629, PMID:23321476, PMID:9845072).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1984 High

    Determining the full-length precursor structure of NPY was essential to understanding how the mature 36-amino acid peptide is generated; cDNA cloning from human pheochromocytoma revealed a 97-aa preproNPY processed at two sites into signal peptide, mature NPY, and a C-terminal peptide.

    Evidence cDNA cloning, nucleotide sequencing, in vitro translation with immunoprecipitation from human pheochromocytoma

    PMID:6589611

    Open questions at the time
    • Processing enzymes responsible for cleavage were not identified
    • Functional role of the C-terminal peptide of NPY (CPON) remained unclear
  2. 1985 High

    How NPY is stored and released in sympathetic nerves was unknown; multiple studies established that NPY is co-stored with noradrenaline in large dense-cored vesicles, transported anterogradely, and acts as a co-transmitter producing vasoconstriction through a non-adrenergic receptor mechanism.

    Evidence Immunohistochemistry, RIA, pharmacological lesions (6-OHDA, reserpine), axonal ligation transport assay, local blood flow measurement with α-adrenoceptor blockade

    PMID:2858824 PMID:2866663

    Open questions at the time
    • The molecular identity of the NPY receptor mediating vasoconstriction was unknown
    • Whether NPY release requires high-frequency versus tonic firing was not yet quantified
  3. 1986 High

    Understanding how NPY gene expression is controlled required knowledge of its genomic structure; the human NPY gene was mapped to four exons spanning ~8 kb, and ~530 bp of 5′ flanking sequence was shown to be sufficient for promoter activity in neuronal cells.

    Evidence Genomic library cloning, primer extension, reporter gene transfection assay in CA-77 and PC12 cells

    PMID:2427515

    Open questions at the time
    • Transcription factor binding sites within the promoter were not functionally dissected
    • Tissue-specific regulatory elements beyond the proximal promoter were not identified
  4. 1990 High

    The rules governing frequency-dependent NPY release and its structure-activity relationships were established: NPY is preferentially released at high stimulation frequencies, auto-inhibits its own release, and requires an intact amidated C-terminus for receptor binding and cAMP inhibition.

    Evidence In vitro organ bath pharmacology, sympathetic nerve stimulation with overflow measurement, receptor binding, cAMP assays across multiple vascular beds

    PMID:2170253

    Open questions at the time
    • Receptor subtypes mediating prejunctional feedback inhibition were not identified
    • Post-release metabolism/inactivation mechanisms for NPY were not addressed
  5. 1995 High

    The molecular identities and signaling properties of the principal NPY receptors were resolved: cloning of Y1 (Gi-coupled, cAMP inhibition, cell-type-dependent Ca²⁺ coupling), Y2 (preferring C-terminal NPY fragments), and Y4 (preferring pancreatic polypeptide) established the receptor family's pharmacological and signaling diversity.

    Evidence Expression cloning, heterologous expression in HEK-293 and CHO cells, radioligand binding, cAMP and intracellular Ca²⁺ assays, pertussis toxin sensitivity

    PMID:1321422 PMID:7493937 PMID:7559383 PMID:7592910

    Open questions at the time
    • Y5 receptor had not yet been cloned
    • Structural basis for subtype-selective ligand recognition was unknown
    • Downstream effectors beyond cAMP/Ca²⁺ were not characterized
  6. 1998 High

    Whether endogenous NPY levels influence ethanol-related behavior was untested; reciprocal genetic models showed that NPY-knockout mice consume more ethanol with reduced sedative sensitivity, while NPY-overexpressing mice show the opposite, establishing an inverse NPY–ethanol relationship.

    Evidence NPY-/- knockout and neuronal NPY-overexpressing transgenic mice, two-bottle ethanol preference, ethanol-induced sleep test

    PMID:9845072

    Open questions at the time
    • Which NPY receptor subtype mediates ethanol-related effects was not determined
    • Brain regional specificity of NPY's anti-ethanol effect was unknown
  7. 2000 High

    The receptor subtype hierarchy for NPY-induced feeding was disputed; Y1-knockout mice showed dramatically reduced NPY-induced feeding while Y5-knockout mice showed only partial attenuation, establishing Y1 as the dominant orexigenic receptor and Y5 as a modulator of energy expenditure and LH secretion.

    Evidence Y1-/- and Y5-/- knockout mice with ICV NPY/selective agonist administration, food intake measurement; separate studies with Y5 agonists measuring BAT temperature and oxygen consumption; Y5 pharmacology for LH suppression

    PMID:10465275 PMID:10564216 PMID:10698177

    Open questions at the time
    • Whether Y1 and Y5 cooperate on the same neurons or distinct circuits was unclear
    • Compensatory receptor upregulation in KO models was not assessed
  8. 2001 High

    The hierarchical relationship between ghrelin, leptin, and NPY in hypothalamic feeding circuits was unknown; ghrelin was shown to activate Fos in NPY/AgRP neurons and require intact NPY/AgRP signaling for its orexigenic effect, while leptin suppresses fasting-induced NPY mRNA via its receptor on arcuate neurons.

    Evidence ICV ghrelin with Fos IHC, anti-NPY/AgRP antibody neutralization, NPY mRNA RT-PCR; leptin infusion in fasted rats and leptin-receptor-mutant models with NPY mRNA quantification

    PMID:11196643 PMID:11737554

    Open questions at the time
    • Direct electrophysiological confirmation of ghrelin-to-NPY neuron activation was pending
    • Intracellular signaling cascade from ghrelin receptor to NPY transcription was unresolved
  9. 2003 High

    How ghrelin signal transduction reaches NPY neurons at the single-cell level was resolved: ghrelin directly elevates [Ca²⁺]i in NPY-immunopositive arcuate neurons via PKA and N-type Ca²⁺ channels, with leptin acting as a direct antagonist of this response.

    Evidence Enzymatic dissociation of rat arcuate neurons, fura-2 Ca²⁺ imaging, NPY immunocytochemistry, PKA/PKC inhibitors, N-type/L-type channel blockers

    PMID:12663466

    Open questions at the time
    • Whether ghrelin modulates NPY vesicular release in addition to excitability was untested
    • Downstream transcriptional consequences of the PKA/Ca²⁺ cascade in NPY neurons were not mapped
  10. 2008 High

    Multiple mechanistic advances converged: (1) ghrelin activation of NPY/AgRP neurons requires UCP2-dependent mitochondrial fatty acid oxidation via AMPK/CPT1; (2) an NPY promoter SNP (rs16147) accounts for >50% of in vivo NPY expression variation and predicts amygdala stress reactivity; (3) NPY-Y1 signaling drives adult neurogenesis via ERK1/2 and neuroprotection occurs via Y2 receptors; (4) subtype-specific receptor–peptide contacts were mapped showing the NPY N-terminus engages Y1 but not Y2/Y4.

    Evidence UCP2-KO mice with electrophysiology and mitochondrial assays; haplotype-promoter-reporter assays with fMRI and PET imaging; Y1-KO SVZ neurogenesis quantification and growth cone turning assays; receptor mutagenesis/chimera binding studies

    PMID:18385673 PMID:18412629 PMID:18668043 PMID:18725084 PMID:18725086

    Open questions at the time
    • The full mitochondrial signaling pathway from UCP2 to membrane depolarization in NPY neurons was incompletely characterized
    • Whether the rs16147 promoter variant affects NPY levels in specific brain nuclei was unresolved
    • Structural resolution of receptor–peptide complexes at atomic level was still lacking
  11. 2013 Medium

    How NPY antagonizes the melanocortin system at a post-translational level was unknown; NPY was shown to suppress prohormone convertase-2 (PC2) expression via Y1/Egr-1 signaling, thereby reducing POMC-to-α-MSH processing and α-MSH-induced CREB phosphorylation in hypothalamic neurons.

    Evidence Hypothalamic cell culture and in vivo intra-PVN NPY injection, PC2 mRNA/protein quantification, Egr-1 analysis, CREB phosphorylation Western blot, Y1 antagonist pharmacology

    PMID:23321476

    Open questions at the time
    • Whether this mechanism operates in the arcuate nucleus or only in PVN was unclear
    • The contribution of PC2 suppression versus direct synaptic inhibition to NPY's net anti-melanocortin effect was not quantified
  12. 2017 High

    Whether insulin acts directly on NPY neurons to regulate energy balance was untested; conditional deletion of the insulin receptor specifically in NPY neurons in both mice and Drosophila produced obesity and altered GH/IGF-1 signaling, establishing an evolutionarily conserved insulin–NPY neuronal axis.

    Evidence Conditional insulin receptor knockout in NPY neurons (mouse and Drosophila), metabolic phenotyping including body composition, food intake, energy expenditure, GH/IGF-1 axis assessment

    PMID:28580287

    Open questions at the time
    • Whether insulin directly regulates NPY transcription or only neuronal excitability was not distinguished
    • Interaction between insulin and leptin/ghrelin signaling within NPY neurons was not addressed
  13. 2021 Medium

    A peripheral-to-central regulatory loop for NPY was discovered: skeletal PGE2/EP4 signaling induces the co-repressor SMILE in the hypothalamus, which binds pCREB on the Npy promoter to suppress NPY transcription, linking bone-derived interoception to hypothalamic NPY control of bone and fat metabolism.

    Evidence EP4 conditional KO in sensory neurons, ChIP and co-IP for SMILE–pCREB on Npy promoter, NPY promoter reporter, Y1R antagonist rescue of bone phenotype, osteoblast fatty acid oxidation assay

    PMID:34468315

    Open questions at the time
    • Whether SMILE–pCREB interaction on the Npy promoter operates in all hypothalamic nuclei or is regionally restricted is unknown
    • Independent replication of the skeletal interoceptive pathway is lacking
  14. 2022 High

    Atomic-resolution understanding of NPY–receptor recognition was achieved: cryo-EM structures of Y1, Y2, and Y4 in complex with NPY/PP and Gi1 confirmed that the NPY N-terminus makes extensive contacts with Y1 but not Y2/Y4, providing the structural basis for subtype-selective pharmacology.

    Evidence Cryo-EM structure determination of three receptor–ligand–Gi complexes, site-directed mutagenesis, cAMP and Ca²⁺ functional assays

    PMID:35507650

    Open questions at the time
    • Y5 receptor structure in complex with NPY has not been determined
    • Conformational dynamics of NPY upon receptor binding are not captured by static cryo-EM
    • Structure-guided selective agonist/antagonist design has not yet been validated in vivo

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of Y5 receptor selectivity, the circuit-level integration of insulin/leptin/ghrelin inputs onto individual NPY neurons, the precise mechanism by which UCP2-dependent mitochondrial changes translate to NPY neuronal firing, and whether NPY's peripheral metabolic effects on adipocytes and bone are therapeutically targetable.
  • No Y5 receptor structure available
  • Single-cell resolution of convergent hormonal inputs on NPY neurons is lacking
  • In vivo therapeutic validation of NPY-receptor-selective compounds for metabolic or psychiatric indications is absent

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 6 R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1
Partners
GHSRLEPRNPY1RNPY2RNPY4RNPY5RUCP2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1984 The human NPY gene encodes a 97-amino acid precursor (preproNPY) that undergoes proteolytic processing at two sites to generate three peptides: a 28-aa signal peptide, the 36-aa mature NPY, and a 30-aa C-terminal peptide. The coding sequence was determined from a human pheochromocytoma cDNA. cDNA cloning, nucleotide sequencing, in vitro translation with immunoprecipitation, Edman degradation Proceedings of the National Academy of Sciences of the United States of America High 6589611
1986 The human NPY gene spans ~8 kb and contains four exons: exon 1 is non-translated; exon 2 encodes the signal peptide through residue 63 of preproNPY; exon 3 encodes 27 amino acids; exon 4 encodes the C-terminal heptapeptide and 3′ UTR. A TATA-like and CAAT-like sequence are present 25 and 70 bp upstream of the transcription start site, respectively. Approximately 530 bp of 5′ flanking sequence is sufficient for promoter activity in neuronal cell lines (CA-77, PC12). Genomic library cloning, primer extension, reporter gene (chloramphenicol acetyltransferase) transfection assay The Journal of biological chemistry High 2427515
1987 Synthetic porcine NPY adopts a concentration-independent alpha-helical conformation in aqueous solution at neutral/basic pH (as shown by circular dichroism), with loss of helical content at acidic pH. The peptide is neither wholly monomeric nor dimeric by sedimentation equilibrium, suggesting an intramolecularly stabilized helical structure analogous to avian pancreatic polypeptide. Receptor binding affinity IC50 ~5 nM. Solid-phase peptide synthesis, circular dichroism spectroscopy, sedimentation equilibrium, radioligand receptor binding assay Neuropeptides Medium 2823169
1985 NPY is co-localized with noradrenaline in large dense-cored vesicles of sympathetic perivascular neurons. 6-OHDA treatment depletes NPY-immunoreactivity in terminal regions while increasing it in stellate ganglion cell bodies. Reserpine causes dose- and time-dependent depletion of NPY from sympathetic nerve terminals (heart, spleen) dependent on intact nerve activity, but unlike NA, NPY depletion by reserpine is entirely dependent on ongoing neuronal activity. Axonal ligation reveals anterograde axonal transport of NPY at ~3 mm/h, and reserpine significantly increases this transport rate. Immunohistochemistry, radioimmunoassay, 6-OHDA and reserpine pharmacological lesions, nerve ligation axonal transport assay, HPLC Naunyn-Schmiedeberg's archives of pharmacology High 2858824
1985 NPY is present in sympathetic perivascular nerves of dental pulp and oral mucosa (co-localized with noradrenaline) and produces potent, long-lasting vasoconstriction resistant to alpha-adrenoceptor blockade by phentolamine and unaffected by guanethidine, demonstrating that NPY acts through a receptor mechanism distinct from adrenoceptors to reduce local blood flow. Immunohistochemistry, retrograde axonal tracing, HPLC, local 125I-clearance blood flow measurement, pharmacological antagonism (phentolamine, guanethidine) Acta physiologica Scandinavica High 2866663
1990 NPY co-exists with noradrenaline in large dense-cored vesicles and is preferentially released compared to NA upon high-frequency stimulation or strong reflex sympathetic activation. NPY release is inhibited by prejunctional alpha-2 adrenoceptors and adenosine receptors, and facilitated by angiotensin II or beta-receptor activation. NPY itself exerts prejunctional inhibition of both NA and NPY release. A large amidated C-terminal portion of NPY is necessary for receptor binding, inhibition of cAMP formation, and vasoconstrictor effects. Reserpine-induced NPY synthesis in ganglia is regulated by nicotinic receptor activity. In vitro organ bath pharmacology, sympathetic nerve stimulation, radioimmunoassay of overflow, receptor binding, cAMP assay, pharmacological dissection Fundamental & clinical pharmacology High 2170253
1992 The cloned human NPY Y1 receptor is a G protein-coupled receptor that, when expressed in HEK-293 cells, couples to a pertussis toxin-sensitive Gi protein to inhibit cAMP accumulation. In CHO cells, the same receptor couples instead to elevation of intracellular calcium, demonstrating cell-type-specific second messenger coupling dependent on the available G protein repertoire. cDNA cloning, heterologous expression in CHO and HEK-293 cells, radioligand binding, cAMP assay, intracellular calcium measurement, pertussis toxin treatment Proceedings of the National Academy of Sciences of the United States of America High 1321422
1995 The cloned human NPY Y2 receptor (381 aa, 31% identical to Y1) expressed in HEK-293 and CHO cells binds NPY and PYY with high affinity but binds [Leu31,Pro34]NPY with low affinity, and binds truncated NPY13-36 with high affinity — confirming Y2 pharmacological profile. The Y2 receptor inhibits forskolin-stimulated cAMP and increases intracellular Ca2+ when stably expressed in CHO cells. Expression cloning from hippocampal cDNA library, radioligand binding (125I-PYY), cAMP assay, intracellular calcium measurement in stably transfected CHO cells The Journal of biological chemistry High 7559383 7592910
1995 A novel human NPY receptor (PP1/Y4) with 43% amino acid identity to Y1 was cloned; it binds pancreatic polypeptide with highest affinity (Ki 13.8 pM), PYY with 1.44 nM, and NPY with 9.9 nM — pharmacologically distinguishing it from Y1 and Y2. In stably transfected CHO cells, this receptor inhibits forskolin-stimulated cAMP synthesis via Gi. Homology-based cloning from human cDNA, radioligand binding, cAMP assay in stably transfected CHO cells, Northern blot The Journal of biological chemistry High 7493937
1996 Leptin receptor mRNA co-distributes with NPY-expressing neurons in the ventromedial subdivision of the hypothalamic arcuate nucleus, demonstrated by in situ hybridization of semi-adjacent sections, establishing that leptin receptors are expressed on NPY neurons. In situ hybridization on mouse brain sections with probes for leptin receptor mRNA and NPY mRNA on semi-adjacent sections Neuroreport Medium 9116246
1996 Antisense oligodeoxynucleotides targeting the NPY Y1 receptor mRNA, microinjected into the rat ventromedial hypothalamus, suppress NPY-induced feeding and cause hypothermia and body weight reduction, establishing that Y1 receptors in the VMH are necessary for NPY-induced feeding and thermoregulatory responses. Antisense oligodeoxynucleotide knockdown of Y1R in VMH, food intake measurement, body temperature telemetry, locomotor activity monitoring Proceedings. Biological sciences Medium 8760491
1997 NPY acting on Y2 receptors in the dorsal vagal complex (DVC) mimics PYY's suppression of TRH-stimulated gastric motility, while Y1 receptor activation in the DVC stimulates gastric motility from basal conditions. The direction of NPY's effect on gastric motility depends on which receptor subtype is activated and the basal state of stimulation. Microinjection of selective Y1 and Y2 agonists/antagonists into rat DVC, in vivo gastric motility recording, pharmacological dissection Neurogastroenterology and motility Medium 9198086
1998 NPY-deficient mice (preproNPY knockout) show increased ethanol consumption and reduced sensitivity to the sedative/hypnotic effects of ethanol (faster recovery from ethanol-induced sleep at equivalent plasma ethanol levels). Conversely, transgenic mice overexpressing NPY in neurons show lower ethanol preference and enhanced sedative sensitivity. These results establish an inverse relationship between brain NPY levels and ethanol consumption/resistance. Targeted gene disruption (NPY-/- mice), transgenic NPY overexpression, two-bottle choice ethanol consumption assay, ethanol-induced sleep/loss-of-righting-reflex test, plasma ethanol measurement Nature High 9845072
1999 The inhibitory effect of centrally administered NPY on LH secretion is predominantly mediated by the Y5 receptor subtype: selective Y5 agonists (PYY3-36, human PP, [D-Trp32]NPY) inhibited LH release, while selective Y2 and Y4 agonists did not. A non-peptidic Y5 receptor antagonist (icv, 6–100 μg) dose-dependently blocked NPY-induced LH suppression and also inhibited NPY-stimulated food intake. Intracerebroventricular administration of selective NPY receptor agonists/antagonists in castrated rats, plasma LH RIA, competitive radioligand binding with Y5-specific assay Endocrinology High 10465275
1999 NPY Y5 receptor activation mediates both the feeding response and reductions in energy expenditure: selective Y5 agonist D-[Trp32]-NPY (icv) stimulates food intake, reduces brown adipose tissue temperature, and decreases whole-body oxygen consumption, while Y1-, Y2-, and Y4-selective agonists do not reproduce these metabolic effects. ICV administration of receptor-selective NPY analogs in rats, food intake measurement, implanted BAT temperature transponders, indirect calorimetry The American journal of physiology Medium 10564216
2000 Human adipocytes express Y1 receptor (detected by RT-PCR and high-affinity radioligand binding with Y1-selective probes); Y1 receptor activation by NPY/PYY produces antilipolytic effects and enhances leptin secretion from adipocytes. These effects are blocked by selective Y1 antagonists (SR120819A, BIBP3226) and by pertussis toxin-insensitive GTPγS-binding, confirming Gi-coupled Y1 receptor signaling. RT-PCR, radioligand binding (125I-PYY, 125I-[Leu31,Pro34]PYY), [35S]GTPγS binding, lipolysis assay in isolated human adipocytes, leptin secretion ELISA, selective antagonist pharmacology FEBS letters High 10858507
2000 In goldfish, central (ICV) administration of the Y1-like receptor agonist [Leu31,Pro34]-NPY stimulates food intake to the same extent as NPY, while the Y2 agonist does not; this effect is blocked by the general NPY antagonist NPY(27-36). Furthermore, the opioid antagonist naloxone (ICV) blocks NPY-induced feeding, demonstrating that NPY's orexigenic effect in fish is mediated via Y1-like receptors and requires intact opioidergic signaling. ICV microinjection of selective NPY receptor agonists and antagonists in goldfish, food intake measurement, opioid antagonist (naloxone) pretreatment Peptides Medium 11068096
2000 Y1 receptor knockout mice (Y1-/-) show dramatically reduced NPY-induced food intake after ICV NPY administration, establishing Y1 as the dominant receptor mediating NPY-induced feeding. Y5 receptor knockout mice show only partial reduction of feeding induced by Y5-preferring agonists but not NPY itself. Additionally, food intake induced by Y5-preferring agonists (PYY3-36, human/bovine PP) is reduced in Y1-/- mice, indicating indirect modulation through Y1 signaling. Y1-/- and Y5-/- knockout mouse generation, ICV administration of NPY and receptor-selective analogs, food intake measurement Endocrinology High 10698177
2001 Ghrelin administered ICV strongly stimulates feeding in rats and activates Fos protein in NPY/AgRP neurons in the arcuate nucleus. Antibodies and antagonists against NPY and AgRP abolish ghrelin-induced feeding. Ghrelin augments NPY gene expression in the hypothalamus and blocks leptin-induced feeding suppression, placing NPY downstream of ghrelin and in competitive interaction with leptin in feeding regulation. ICV ghrelin injection, Fos immunohistochemistry, anti-NPY/AgRP antibody neutralization, NPY/AgRP antagonist pharmacology, RT-PCR for NPY mRNA, leptin interaction experiments Nature High 11196643
2001 Fasting increases hypothalamic NPY and AGRP mRNA in parallel when leptin levels fall; leptin infusion (48 h via subcutaneous osmotic pump) in fasted lean rats almost completely reverses fasting-induced increases in both NPY and AGRP mRNA and restores POMC mRNA. In contrast, leptin-receptor-deficient Zucker (fa/fa) rats show upregulation of NPY but not AGRP mRNA, demonstrating that leptin acts via its receptor on arcuate neurons to suppress NPY expression. Solution hybridization/S1 nuclease protection assay for hypothalamic NPY, AGRP, POMC mRNA; subcutaneous leptin infusion; leptin receptor mutant rat models (Koletsky, Zucker fa/fa) Journal of neuroendocrinology High 11737554
2002 Antidepressant-like activity of ICV NPY in the mouse forced swimming test is mediated via the Y1 receptor subtype: the Y1 agonist [Leu31,Pro34]PYY mimics NPY's anti-immobility effect; Y1 antagonists (BIBO3304, BIBP3226) block NPY's effect; Y2 agonist NPY(13-36) has no anti-immobility effect at tested doses; Y2 antagonist BIIE0246 is active but may reflect locomotor changes. ICV drug administration in mice, forced swimming test (immobility time), open field locomotor activity measurement, receptor-selective agonist/antagonist pharmacology Neuropsychopharmacology Medium 11927186
2003 Ghrelin directly activates NPY neurons in the rat arcuate nucleus via Ca2+ signaling: single isolated ARC neurons respond to ghrelin (10-12–10-8 mol/L) with increased [Ca2+]i; ~80% of ghrelin-responsive neurons are NPY-immunopositive. The Ca2+ response is blocked by PKA inhibitors but not PKC inhibitors, and by N-type but not L-type Ca2+ channel blockers. Leptin attenuates ghrelin-induced Ca2+ increases in NPY neurons; orexin is additive with ghrelin. Enzymatic dissociation of rat ARC neurons, fura-2 single-cell Ca2+ imaging, immunocytochemical NPY identification, selective kinase inhibitors and channel blockers, glucose-sensing neuron identification Diabetes High 12663466
2003 Chronic ICV infusion of the selective Y5 agonist D-Trp34NPY in C57BL/6J mice produces hyperphagia, obesity, increased adiposity, hyperinsulinemia, hyperleptinemia, and hypercholesterolemia; all effects are fully blocked by oral administration of a selective Y5 antagonist. Under pair-feeding, Y5 activation still reduces hormone-sensitive lipase activity in white adipose tissue and decreases UCP-1 mRNA in brown adipose tissue, indicating that Y5-mediated obesity involves both hyperphagia and metabolic changes (decreased lipolysis and thermogenesis). ICV infusion via osmotic minipump, pair-feeding paradigm, selective Y5 antagonist oral dosing, adipose tissue enzyme activity assay, UCP-1 RT-PCR Endocrinology High 12697685
2003 NPY suppresses experimental autoimmune encephalomyelitis (EAE) via Y1 receptors: exogenous NPY and Y1 receptor agonists significantly inhibit EAE induction, while Y5 agonist or combined NPY + Y1 antagonist treatment does not. Y1 antagonist alone produces earlier EAE onset, demonstrating a protective role of endogenous NPY. The Y1 agonist inhibits myelin oligodendrocyte glycoprotein-specific Th1 responses and biases autoimmune T cells toward Th2, directly affecting T cells through Y1 receptors. Active EAE induction in C57BL/6 mice, selective NPY receptor agonist/antagonist treatment, clinical disease scoring, ex vivo T cell cytokine profiling, antigen-specific proliferation assay Journal of immunology High 14500640
2008 NPY molecular recognition by Y receptors involves distinct binding poses: one conserved aspartate residue in the third extracellular loop is essential for ligand binding across all four Y receptors (Y1, Y2, Y4, Y5) but interacts with different arginine residues in the ligand depending on receptor subtype. The N terminus of NPY forms extensive interactions with Y1 but not with Y2 or Y4 receptors. These subtype-specific contacts were mapped by combining chemically modified peptide analogs, receptor mutagenesis, and chimeric receptors. Receptor mutagenesis (site-directed), chimeric receptor construction, peptide analog synthesis with chemical modifications, radioligand binding in transfected cells Nutrition High 18725086
2008 Ghrelin activates NPY/AgRP neurons through a UCP2-dependent mitochondrial mechanism. Ghrelin induces hypothalamic mitochondrial proliferation and electrical activation of NPY/AgRP neurons; these effects require UCP2. The UCP2-dependent mechanism is driven by a fatty acid oxidation pathway involving AMPK and CPT1, which generates free radicals that are scavenged by UCP2, thereby altering mitochondrial respiration and NPY/AgRP neuronal excitability. Ghrelin-triggered synaptic plasticity of POMC neurons and ghrelin-induced food intake are also UCP2-dependent. UCP2 knockout mice, hypothalamic mitochondrial respiration assays, AMPK and CPT1 pharmacological inhibitors, electrophysiology of NPY/AgRP neurons, reactive oxygen species measurement, electron microscopy of mitochondria, synaptic plasticity assay Nature High 18668043
2008 A SNP (rs16147) in the NPY promoter region alters NPY expression in vitro and accounts for more than half of the in vivo variation in NPY mRNA levels driven by haplotype. Lower haplotype-driven NPY expression predicts higher amygdala activation to emotional stimuli and diminished stress resilience (reduced endogenous opioid neurotransmission during pain/stress). NPY haplotypes predict plasma NPY levels and lymphoblast NPY mRNA levels. Haplotype analysis, in vitro promoter-reporter assay (SNP rs16147), post-mortem brain NPY mRNA quantification, lymphoblast mRNA, plasma NPY RIA, fMRI amygdala activation, PET endogenous opioid neurotransmission Nature High 18385673
2008 NPY promotes chemokinesis of dorsal root ganglion growth cones via an attractive turning response and increased growth rate mediated by the Y1 receptor, as demonstrated by asymmetric gradient application of NPY to cultured embryonic DRG neurons. Y1 receptor-deficient mice have fewer proliferating precursor cells and neuroblasts in the subventricular zone and rostral migratory stream and fewer neurons in the olfactory bulb, linking NPY-Y1 signaling to adult neurogenesis. Asymmetric NPY gradient application to embryonic DRG growth cone cultures (turning assay), Y1 and Y2 receptor knockout mouse analysis, SVZ/RMS BrdU proliferation assay, olfactory bulb neuron counting Nutrition High 18725084
2008 Exogenous NPY Y2 receptor activation (NPY13-36, 300 nM) provides neuroprotection against AMPA-induced excitotoxicity in CA1 and CA3 pyramidal cells of mouse organotypic hippocampal slices, blocked by Y2 antagonist BIIE0246. Endogenous NPY provides additional neuroprotection revealed by Y1 antagonist (BIBP3226) or NPY-neutralizing antibody treatment. AMPA-induced neurodegeneration is associated with microglial BDNF release and upregulation of neuronal TrkB; this BDNF is not required for NPY Y2-mediated neuroprotection. Organotypic hippocampal slice culture, AMPA excitotoxicity model, propidium iodide uptake assay, selective Y1/Y2 receptor pharmacology, ELISA for BDNF, immunohistochemistry for TrkB and microglia The European journal of neuroscience Medium 18412629
2011 NPY promotes SVZ cell proliferation (neuroproliferation) and chemokinesis in rats via Y1 receptor-mediated activation of the ERK1/2 MAP kinase pathway, as established by pharmacological approaches. NPY is endogenously synthesized by SVZ cells, suggesting autocrine/paracrine action. NPY does not affect self-renewal of SVZ stem cells. SVZ cell culture, BrdU proliferation assay, pharmacological Y1 receptor antagonism, ERK1/2 pathway inhibitors and Western blot, chemokinesis assay, endogenous NPY synthesis confirmed by RT-PCR/immunostaining Journal of neurochemistry Medium 21175616
2013 NPY inhibits posttranslational processing of POMC to α-MSH by decreasing prohormone convertase-2 (PC2) expression in hypothalamic cells, mediated through Y1 receptors and the transcription factor Egr-1. Intra-PVN NPY also decreases PC2 in PVN samples, reducing pro-TRH processing. Additionally, NPY attenuates α-MSH-induced TRH production by (1) decreasing α-MSH-induced CREB phosphorylation, and (2) reducing α-MSH levels in the PVN. Hypothalamic cell culture and in vivo intra-PVN injection, PC2 protein/mRNA quantification, Egr-1 transcription factor analysis, CREB phosphorylation Western blot, α-MSH and TRH peptide measurements, Y1 receptor antagonist pharmacology American journal of physiology. Endocrinology and metabolism Medium 23321476
2016 NPY promotes intestinal epithelial cell proliferation and reduces apoptosis via PI3K-β-catenin signaling and downregulation of miR-375. In NPY knockout mice, inflammation-induced tumorigenesis (DSS model) produces fewer and smaller polyps with reduced proliferation (PCNA, Ki67) and increased apoptosis (TUNEL) compared to wild-type. In vitro, NPY increases PCNA, β-catenin, c-Myc, and cyclin D1, and reduces p21 in epithelial cell lines. miR-375 inhibitor does not further enhance NPY-treated cells, indicating miR-375 acts downstream of NPY. NPY-/- knockout mice, DSS colitis-associated tumorigenesis model, intestinal epithelial cell lines (T84), PCNA/Ki67 IHC, TUNEL apoptosis assay, PI3K pathway inhibitors, β-catenin Western blot, miR-375 qRT-PCR, miR-375 inhibitor epistasis American journal of physiology. Gastrointestinal and liver physiology Medium 27856419
2016 Systemic NPY dose-dependently inhibits dural-evoked trigeminovascular neuronal firing in rat trigeminocervical complex (TCC) through Y1 receptor activation: the Y1 agonist reproduces NPY's inhibitory effect, while Y2 and Y5 agonists and the Y1 antagonist have no significant effect, establishing NPY as an antinociceptive peptide in the trigeminovascular system acting via Y1 receptors. In vivo electrophysiology in anesthetized rats (TCC neuronal recording), dural nociceptive stimulation, systemic NPY and receptor-selective agonist/antagonist administration Pain Medium 27023421
2017 Insulin signaling specifically in NPY neurons controls food intake and energy expenditure: genetic deletion of the insulin receptor in NPY neurons (in both flies and mice) leads to increased energy stores, obesity, dysregulation of the GH/IGF-1 axis, and altered insulin sensitivity. This establishes an ancient insulin/NPY neuronal network governing energy homeostasis across phyla. Conditional insulin receptor knockout specifically in NPY neurons (mouse and Drosophila), food intake and energy expenditure measurements, body composition analysis, GH/IGF-1 axis assessment, insulin sensitivity testing Molecular metabolism High 28580287
2021 Ascending skeletal interoceptive signaling (via PGE2/EP4) downregulates hypothalamic NPY expression: EP4 activation induces SMILE (small heterodimer partner-interacting leucine zipper protein) in the hypothalamus, which binds pCREB as a transcriptional heterodimer on Npy promoters to inhibit NPY expression. Knockout of EP4 in sensory nerves increases NPY, causing bone catabolism and fat anabolism. Inhibition of NPY Y1R accelerates free fatty acid oxidation in osteoblasts and rescues bone loss. EP4 conditional KO in sensory neurons, hypothalamic SMILE expression, ChIP/co-IP showing SMILE-pCREB interaction at Npy promoter, NPY promoter reporter assay, Y1R antagonist treatment, osteoblast fatty acid oxidation assay, bone phenotype analysis eLife Medium 34468315
2022 Cryo-EM structures of human Y1, Y2, and Y4 receptors in complex with NPY or pancreatic polypeptide and Gi1 protein reveal that the N-terminus of NPY forms extensive interactions specifically with Y1 but not with Y2 or Y4. Different receptors impose distinct binding poses on the peptide, reflecting conformational plasticity of NPY. Mutagenesis and functional studies confirmed subtype-specific receptor-peptide contacts, providing a structural basis for selective drug development. Cryo-EM structure determination, site-directed mutagenesis, functional signaling assays (cAMP, calcium), ligand binding assays Science advances High 35507650

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 A role for ghrelin in the central regulation of feeding. Nature 2747 11196643
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 589 18668043
2004 The NPY system in stress, anxiety and depression. Neuropeptides 474 15337373
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1992 Cloned human neuropeptide Y receptor couples to two different second messenger systems. Proceedings of the National Academy of Sciences of the United States of America 416 1321422
1998 Ethanol consumption and resistance are inversely related to neuropeptide Y levels. Nature 374 9845072
2012 Neuropeptide Y, peptide YY and pancreatic polypeptide in the gut-brain axis. Neuropeptides 366 22979996
2008 Genetic variation in human NPY expression affects stress response and emotion. Nature 332 18385673
2003 Ghrelin directly interacts with neuropeptide-Y-containing neurons in the rat arcuate nucleus: Ca2+ signaling via protein kinase A and N-type channel-dependent mechanisms and cross-talk with leptin and orexin. Diabetes 305 12663466
2002 The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y. Neuroscience and biobehavioral reviews 283 12034130
1984 Cloning, characterization, and DNA sequence of a human cDNA encoding neuropeptide tyrosine. Proceedings of the National Academy of Sciences of the United States of America 276 6589611
1995 Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY. The Journal of biological chemistry 274 7493937
1995 Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype. The Journal of biological chemistry 237 7592910
1995 Cloning and functional expression of a cDNA encoding a human type 2 neuropeptide Y receptor. The Journal of biological chemistry 234 7559383
2004 NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 229 15337371
2010 Poor replication of candidate genes for major depressive disorder using genome-wide association data. Molecular psychiatry 220 20351714
2010 Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO molecular medicine 210 20972986
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2000 Role of the Y1 receptor in the regulation of neuropeptide Y-mediated feeding: comparison of wild-type, Y1 receptor-deficient, and Y5 receptor-deficient mice. Endocrinology 199 10698177
2009 Classification of NPY-expressing neocortical interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 193 19295167
2013 Exploring the genetic basis of chronic periodontitis: a genome-wide association study. Human molecular genetics 188 23459936
2003 The DNA sequence of human chromosome 7. Nature 188 12853948
2002 The neuropeptide Y (NPY) Y1 receptor subtype mediates NPY-induced antidepressant-like activity in the mouse forced swimming test. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 173 11927186
2000 Low baseline and yohimbine-stimulated plasma neuropeptide Y (NPY) levels in combat-related PTSD. Biological psychiatry 170 10715359
2004 Molecular evolution of NPY receptor subtypes. Neuropeptides 169 15337367
2001 The NPY/AgRP neuron and energy homeostasis. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 169 11840217
2001 Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. Journal of neuroendocrinology 167 11737554
2009 A systematic meta-analysis of genetic association studies for diabetic retinopathy. Diabetes 164 19587357
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2009 Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling. Gut 157 19240061
2003 Human chromosome 7: DNA sequence and biology. Science (New York, N.Y.) 154 12690205
1996 Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus--relationship with NPY neurones. Neuroreport 145 9116246
2008 Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. Journal of neuroimmunology 141 18603306
2010 Family-based analysis of genetic variation underlying psychosis-inducing effects of cannabis: sibling analysis and proband follow-up. Archives of general psychiatry 138 21041608
2004 Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides 138 15337374
2009 Genetical genomic determinants of alcohol consumption in rats and humans. BMC biology 135 19874574
2015 The role of NPY in learning and memory. Neuropeptides 132 26454711
1985 Differential effects of reserpine and 6-hydroxydopamine on neuropeptide Y (NPY) and noradrenaline in peripheral neurons. Naunyn-Schmiedeberg's archives of pharmacology 128 2858824
2013 Aberrant methylation of NPY, PENK, and WIF1 as a promising marker for blood-based diagnosis of colorectal cancer. BMC cancer 126 24289328
2006 Physiology and gene regulation of the brain NPY Y1 receptor. Frontiers in neuroendocrinology 122 16989896
2010 Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Molecular psychiatry 121 20308990
2002 A functional neuropeptide Y Leu7Pro polymorphism associated with alcohol dependence in a large population sample from the United States. Archives of general psychiatry 121 12215082
1986 Characterization, sequence, and expression of the cloned human neuropeptide Y gene. The Journal of biological chemistry 121 2427515
2017 Insulin controls food intake and energy balance via NPY neurons. Molecular metabolism 116 28580287
2013 Emerging neuropeptide targets in inflammation: NPY and VIP. American journal of physiology. Gastrointestinal and liver physiology 116 23538492
2016 Neuropeptide Y (NPY) as a therapeutic target for neurodegenerative diseases. Neurobiology of disease 111 27461050
1990 Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fundamental & clinical pharmacology 109 2170253
2003 Neuropeptide Y (NPY) Y2 receptors mediate behaviour in two animal models of anxiety: evidence from Y2 receptor knockout mice. Behavioural brain research 105 12742262
1994 Preference and diet type affect macronutrient selection after morphine, NPY, norepinephrine, and deprivation. The American journal of physiology 105 8141399
2000 Nicotine administration enhances NPY expression in the rat hypothalamus. Brain research 101 10837809
2007 NPY and receptors in immune and inflammatory diseases. Current topics in medicinal chemistry 98 17979783
2001 Origins of the many NPY-family receptors in mammals. Peptides 98 11287083
2002 Hypothalamic NPY, AGRP, and POMC mRNA responses to leptin and refeeding in mice. American journal of physiology. Regulatory, integrative and comparative physiology 94 12376393
1986 Topography of NPY-, somatostatin-, and VIP-immunoreactive, neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion and their projection to the pylorus. The Journal of neuroscience : the official journal of the Society for Neuroscience 92 2875137
2009 Neuropeptide Y (NPY) gene: Impact on emotional processing and treatment response in anxious depression. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology 90 19854625
2002 Brain neuropeptide Y (NPY) in stress and alcohol dependence. Reviews in the neurosciences 90 12013027
1999 Evidence that the inhibition of luteinizing hormone secretion exerted by central administration of neuropeptide Y (NPY) in the rat is predominantly mediated by the NPY-Y5 receptor subtype. Endocrinology 85 10465275
2003 Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo. Journal of immunology (Baltimore, Md. : 1950) 81 14500640
2016 Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response. Cell metabolism 80 27411010
1985 Neuropeptide Y (NPY) and sympathetic control of blood flow in oral mucosa and dental pulp in the cat. Acta physiologica Scandinavica 80 2866663
1997 PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the DVC. Neurogastroenterology and motility 75 9198086
2018 Cellular and synaptic reorganization of arcuate NPY/AgRP and POMC neurons after exercise. Molecular metabolism 74 30292523
1999 Activation of the NPY Y5 receptor regulates both feeding and energy expenditure. The American journal of physiology 73 10564216
2009 Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology 67 20012021
2006 Spinal mechanisms of NPY analgesia. Peptides 67 17194506
1996 Antisense to NPY-Y1 demonstrates that Y1 receptors in the hypothalamus underlie NPY hypothermia and feeding in rats. Proceedings. Biological sciences 65 8760491
1989 Ultrastructural features of NPY-containing neurons in the rat striatum. Brain research 65 2702486
2012 Dorsomedial hypothalamic NPY and energy balance control. Neuropeptides 64 23083763
2003 'Neuro'-peptides in glia: focus on NPY and galanin. Trends in neurosciences 64 14585600
1998 Neuropeptide Y (NPY) Y1 receptor mRNA is upregulated in association with transient hyperphagia and body weight gain: evidence for a hypothalamic site for concurrent development of leptin resistance. Journal of neuroendocrinology 64 9510057
2000 Food intake regulation in rodents: Y5 or Y1 NPY receptors or both? Canadian journal of physiology and pharmacology 60 10737680
2000 NPY receptors and opioidergic system are involved in NPY-induced feeding in goldfish. Peptides 60 11068096
2017 The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. International review of neurobiology 59 29056151
2008 Molecular recognition of the NPY hormone family by their receptors. Nutrition (Burbank, Los Angeles County, Calif.) 58 18725086
2000 Characterization of NPY receptors controlling lipolysis and leptin secretion in human adipocytes. FEBS letters 58 10858507
1999 Galanin and NPY, two peptides with multiple putative roles in the nervous system. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 57 10422730
2008 NPY and its involvement in axon guidance, neurogenesis, and feeding. Nutrition (Burbank, Los Angeles County, Calif.) 56 18725084
2018 Postmenopausal osteoporosis is associated with the regulation of SP, CGRP, VIP, and NPY. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 55 29807224
2014 Betahistine ameliorates olanzapine-induced weight gain through modulation of histaminergic, NPY and AMPK pathways. Psychoneuroendocrinology 55 24992721
2006 Behavioral profiling of NPY in aggression and neuropsychiatric diseases. Peptides 55 17196302
2007 The Y1 receptor for NPY: a key modulator of the adaptive immune system. Peptides 54 17240480
2009 Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol (Fayetteville, N.Y.) 51 19913192
2022 Receptor-specific recognition of NPY peptides revealed by structures of NPY receptors. Science advances 47 35507650
2008 Interaction between neuropeptide Y (NPY) and brain-derived neurotrophic factor in NPY-mediated neuroprotection against excitotoxicity: a role for microglia. The European journal of neuroscience 47 18412629
2007 NPY and cardiac diseases. Current topics in medicinal chemistry 47 17979778
2004 Neuropeptide Y (NPY). Pulmonary pharmacology & therapeutics 47 15219262
1994 Perivascular neuropeptides (NPY, VIP, CGRP and SP) in human brain vessels after subarachnoid haemorrhage. Acta neurologica Scandinavica 47 7534026
2015 Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology. Neuropeptides 46 26549645
1998 Neural substrates for leptin and neuropeptide Y (NPY) interaction: hypothalamic sites associated with inhibition of NPY-induced food intake. Physiology & behavior 46 9748101
1987 The synthesis, physical characterization and receptor binding affinity of neuropeptide Y (NPY). Neuropeptides 46 2823169
2007 NPY family of hormones: clinical relevance and potential use in gastrointestinal disease. Current topics in medicinal chemistry 45 17979780
2006 CCK and NPY as anti-anxiety treatment targets: promises, pitfalls, and strategies. Amino acids 45 16738800
2003 Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice: chronic intracerebroventricular infusion of D-Trp(34)NPY. Endocrinology 45 12697685
2006 Gene therapy in epilepsy: the focus on NPY. Peptides 44 17196301
2016 Neuropeptide Y inhibits the trigeminovascular pathway through NPY Y1 receptor: implications for migraine. Pain 43 27023421
2021 NPY and Gene Therapy for Epilepsy: How, When,... and Y. Frontiers in molecular neuroscience 42 33551745
2011 NPY promotes chemokinesis and neurogenesis in the rat subventricular zone. Journal of neurochemistry 42 21175616
2010 Central administration of NPY or an NPY-Y5 selective agonist increase in vivo extracellular monoamine levels in mesocorticolimbic projecting areas. Neuropharmacology 41 20868698
1996 Role of NPY neurones in GH-dependent feedback signalling to the brain. Hormone research 41 8805021
2014 NPY/Y₁ receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension. British journal of pharmacology 40 24779394
1998 The NPY Y1 receptor antagonist BIBP 3226 blocks NPY induced feeding via a non-specific mechanism. Regulatory peptides 40 9802432
1995 Catecholamine and NPY efferents from the ventrolateral medulla to the amygdala in the rat. Brain research bulletin 40 7496819
2000 The role of NPY in metabolic homeostasis: implications for obesity therapy. Expert opinion on investigational drugs 39 11060746
2021 Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY. eLife 38 34468315
2006 Polymorphisms in the NPY and AGRP genes and body fatness in Dutch adults. International journal of obesity (2005) 38 16568137
1997 Pharmacological characterization and selectivity of the NPY antagonist GR231118 (1229U91) for different NPY receptors. Regulatory peptides 38 9652970
2012 Bone-specific overexpression of NPY modulates osteogenesis. Journal of musculoskeletal & neuronal interactions 36 23196263
2007 Neuropeptide Y (NPY) in alcohol intake and dependence. Peptides 36 17239487
1998 Is there really an NPY Y3 receptor? Regulatory peptides 36 9802395
2013 Mechanisms by which the orexigen NPY regulates anorexigenic α-MSH and TRH. American journal of physiology. Endocrinology and metabolism 34 23321476
2009 Appetitive and consummatory ingestive behaviors stimulated by PVH and perifornical area NPY injections. American journal of physiology. Regulatory, integrative and comparative physiology 34 19193934
2007 NPY Y1 receptor antagonist prevents NPY-induced torpor-like hypothermia in cold-acclimated Siberian hamsters. American journal of physiology. Regulatory, integrative and comparative physiology 34 17989140
1989 Neuropeptide Y (NPY) and vasopressin (AVP) in the hypothalamo-neurohypophysial axis of salt-loaded or Brattleboro rats. Brain research 34 2731031
2012 Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence. Neuropeptides 32 22938859
2013 NPY mediates reward activity of morphine, via NPY Y1 receptors, in the nucleus accumbens shell. Behavioural brain research 31 23511250
2002 Appetite suppression based on selective inhibition of NPY receptors. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity 31 11896483
2021 Effect of depression and suicidal behavior on neuropeptide Y (NPY) and its receptors in the adult human brain: A postmortem study. Progress in neuro-psychopharmacology & biological psychiatry 30 34411658
2016 Neuropeptide Y (NPY) promotes inflammation-induced tumorigenesis by enhancing epithelial cell proliferation. American journal of physiology. Gastrointestinal and liver physiology 30 27856419
1999 Parasites flicking the NPY gene on the host's switchboard: why NPY? FASEB journal : official publication of the Federation of American Societies for Experimental Biology 30 10544180
2007 Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calcium. Canadian journal of physiology and pharmacology 29 17487244
2021 The Roles of Neuropeptide Y (Npy) and Peptide YY (Pyy) in Teleost Food Intake: A Mini Review. Life (Basel, Switzerland) 28 34200824
1993 Centrally administered neuropeptide Y (NPY) inhibits gastric emptying and intestinal transit in the rat. Digestive diseases and sciences 28 8482183
2012 The NPY system and its neural and neuroendocrine regulation of bone. Current osteoporosis reports 26 22477260
2005 Characterization of NPY receptor subtypes Y2 and Y7 in rainbow trout Oncorhynchus mykiss. Peptides 26 16359756
1999 Hypothalamic NPY status during positive energy balance and the effects of the NPY antagonist, BW 1229U91, on the consumption of highly palatable energy-rich diet. Peptides 26 10447095
2014 Effect of Acetaldehyde Intoxication and Withdrawal on NPY Expression: Focus on Endocannabinoidergic System Involvement. Frontiers in psychiatry 25 25324788
2003 Neuropeptide Y (NPY) family of hormones: progress in the development of receptor selective agonists and antagonists. Current pharmaceutical design 25 12769744