Affinage

NPY

Pro-neuropeptide Y · UniProt P01303

Length
97 aa
Mass
10.9 kDa
Annotated
2026-06-10
100 papers in source corpus 26 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NPY is a sympathetic and central neuropeptide that couples neuronal activity to feeding, energy balance, autonomic control, and tissue proliferation by acting through a family of Gi/Go-coupled Y receptors (PMID:2170253, PMID:35507650). In sympathetic neurons NPY is co-stored with noradrenaline in large dense-cored vesicles, transported axonally at rapid rates, and released preferentially during high-frequency or strong sympathetic activation; its amidated C-terminus is required for receptor binding, cAMP inhibition, and vasoconstrictor effects, and it acts both prejunctionally to inhibit transmitter release and postjunctionally to potentiate vasoconstriction (PMID:2858824, PMID:2170253). Structural and mutagenesis studies define how NPY engages the Y1, Y2, and Y4 receptors with distinct binding poses, with a conserved third-extracellular-loop aspartate essential across all subtypes engaging different ligand arginines depending on receptor subtype (PMID:35507650, PMID:18725084). Receptor subtype dictates physiology: Y1 signaling mediates antidepressant-like behavior, NTS vasodepressor responses, torpor, suppression of trigeminovascular firing, and suppression of binge alcohol drinking via a Gi/PKA-dependent enhancement of inhibition onto BNST CRF neurons (PMID:11927186, PMID:8221064, PMID:17989140, PMID:27023421, PMID:25751534); presynaptic Y2 receptors suppress excitatory and inhibitory synaptic transmission in the amygdala and confer hippocampal neuroprotection (PMID:26365505, PMID:18412629); and Y5 receptors drive feeding and reduced energy expenditure (PMID:10564216). In the hypothalamus NPY expression in AgRP neurons is uniquely required to sustain hunger after AgRP neuron activation and is transcriptionally repressed by a SMILE–pCREB complex downstream of skeletal interoceptive EP4 signaling, while insulin receptor signaling within NPY neurons governs energy stores and the GH/IGF-1 axis (PMID:31033437, PMID:34468315, PMID:28580287). Beyond neuronal signaling, NPY promotes epithelial and precursor cell proliferation, driving intestinal epithelial growth via PI3-K/β-catenin signaling with miR-375 downregulation and Y1-dependent neuroproliferation (PMID:27856419, PMID:20211262).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1985 Medium

    Established NPY as an axonally trafficked sympathetic neuropeptide whose storage and depletion behavior is distinct from noradrenaline, raising the question of how it is released.

    Evidence Sciatic nerve ligation, reserpine/6-OHDA pharmacology, RIA and IHC in peripheral sympathetic neurons

    PMID:2858824

    Open questions at the time
    • Did not define release kinetics or receptor targets
    • Vesicular storage with noradrenaline inferred pharmacologically
  2. 1990 Medium

    Defined NPY as a sympathetic co-transmitter released at high stimulation frequencies acting pre- and postjunctionally, and identified the amidated C-terminus as the functional binding determinant.

    Evidence Sympathetic nerve stimulation in vascular preparations, pre/postjunctional pharmacology, cAMP assay across multiple vascular beds

    PMID:2170253

    Open questions at the time
    • Receptor subtype assignments not yet molecular
    • Did not resolve atomic basis of receptor engagement
  3. 1993 High

    Demonstrated that Y1 and Y2 receptors exert opposite effects on the same target, establishing subtype-specific and antagonistic NPY signaling in autonomic circuits.

    Evidence Patch-clamp of nodose ganglion Ca2+ currents with subtype-selective agonists; NTS microinjection with blood pressure/heart rate readouts

    PMID:8221064 PMID:8395583

    Open questions at the time
    • Receptor localization (pre- vs postsynaptic) not resolved
    • Downstream effectors not defined
  4. 1997 Medium

    Showed NPY/PYY gastric motility effects are state-dependent and split between Y1 and Y2 receptors, with DPP-IV conversion biasing PYY toward Y2 action.

    Evidence DVC microinjection of receptor-selective agonists with in vivo gastric motility measurement

    PMID:9198086

    Open questions at the time
    • Cellular circuit underlying motility state-dependence undefined
    • No structural basis for ligand selectivity
  5. 2000 High

    Identified Y5-Gi coupled cross-talk with alpha-adrenergic signaling in cardiomyocytes and Y1-mediated antilipolytic/leptin-stimulating action in adipocytes, extending NPY signaling to peripheral metabolic and cardiac targets.

    Evidence Cardiomyocyte cultures with pertussis toxin and MAPK/PKC readouts; adipocyte radioligand binding, GTPγS, lipolysis and leptin assays with Y1 antagonists

    PMID:10660688 PMID:10858507

    Open questions at the time
    • Physiological relevance in vivo not established in these studies
    • Y5 versus Y1 selectivity tissue-dependent
  6. 2001 Medium

    Revealed autocrine/paracrine NPY action enhancing catecholamine secretion in chromaffin cells and Y1-dependent potentiation of vasopressin/oxytocin release, showing NPY amplifies neuroendocrine output.

    Evidence RT-PCR, calcium imaging, immunoneutralization in chromaffin cells; perifused hypothalamo-neurohypophysial explants with selective agonists

    PMID:11124136 PMID:11739470

    Open questions at the time
    • Putative y3 receptor identity uncertain
    • Single-lab findings without reciprocal validation
  7. 2002 Medium

    Mapped Y1-receptor protein to peripheral sensory axons co-localizing with CGRP and pinned antidepressant-like behavioral effects to the Y1 subtype.

    Evidence IHC with nerve crush/rhizotomy axonal transport paradigm; ICV ligand pharmacology in the forced swimming test

    PMID:11869028 PMID:11927186

    Open questions at the time
    • Circuit linking sensory Y1R to nociception not defined
    • Behavioral receptor assignment from pharmacology only
  8. 2003 Medium

    Extended NPY signaling to immune regulation, showing Y1 receptors on autoreactive T cells bias toward Th2 and suppress autoimmune neuroinflammation.

    Evidence EAE induction in mice with Y1/Y5 agonist and antagonist treatment, ex vivo T cell restimulation and cytokine profiling

    PMID:14500640

    Open questions at the time
    • Direct vs indirect T cell action not fully separated
    • Single-lab pharmacological epistasis
  9. 2007 Medium

    Established Y1 receptor as necessary and sufficient for NPY-induced torpor, separating thermoregulatory control from Y5-mediated feeding.

    Evidence ICV receptor-selective agonist/antagonist with body temperature telemetry in Siberian hamsters

    PMID:17989140

    Open questions at the time
    • Effector circuit downstream of Y1R undefined
    • Species-specific torpor model
  10. 2008 Medium

    Defined the conserved aspartate–arginine binding contact for ligand engagement and showed NPY drives neuroprotection and neuroproliferation/axon guidance through Y1 and Y2 receptors.

    Evidence Receptor mutagenesis/chimeras and peptide analogs; growth cone turning assays and Y1/Y2 knockout analysis; hippocampal slice excitotoxicity model with receptor blockers

    PMID:18412629 PMID:18725084

    Open questions at the time
    • Atomic structure of binding not yet resolved at this stage
    • Neuroprotective downstream effectors only partly defined
  11. 2014 Medium

    Connected Y1 signaling to vascular smooth muscle proliferation and vasoconstriction via p38/PKD, implicating NPY in pulmonary hypertension.

    Evidence Myography, calcium imaging, Western blot and proliferation assays in human pulmonary arterial smooth muscle with selective Y1 antagonist

    PMID:24779394

    Open questions at the time
    • Causal role in disease progression in vivo not shown
    • Single-lab study
  12. 2015 High

    Localized Y2 receptors presynaptically in the amygdala and defined a Y1-Gi/PKA postsynaptic mechanism onto BNST CRF neurons controlling binge drinking.

    Evidence Patch-clamp electrophysiology, tract tracing, Y2 knockout mice; chemogenetics and pharmacology across mice and monkeys

    PMID:25751534 PMID:26365505

    Open questions at the time
    • Long-term circuit remodeling after chronic alcohol incompletely mapped
    • Y2 presynaptic target neurons partly undefined
  13. 2017 Medium

    Showed insulin receptor signaling within NPY neurons is a cell-autonomous regulator of energy stores, obesity, and the GH/IGF-1 axis, conserved across flies and mice.

    Evidence Cell-type-specific insulin receptor knockout in NPY neurons with metabolic phenotyping in Drosophila and mouse

    PMID:28580287

    Open questions at the time
    • Downstream transcriptional response in NPY neurons not defined
    • Link to NPY peptide output not directly measured
  14. 2019 High

    Demonstrated NPY peptide itself is uniquely required to sustain hunger driven by AgRP neurons, distinguishing it from co-expressed AgRP and GABA.

    Evidence Cell-type-specific NPY deletion plus re-expression rescue with optogenetic feeding readout

    PMID:31033437

    Open questions at the time
    • Receptor subtype mediating sustained hunger not identified here
    • Temporal dynamics of NPY release undefined
  15. 2021 Medium

    Identified the SMILE–pCREB transcriptional complex repressing hypothalamic Npy downstream of skeletal interoceptive EP4 signaling, linking bone-derived signals to NPY-mediated metabolic control.

    Evidence EP4 sensory nerve knockout mice, promoter binding analysis, Y1R inhibition and bone phenotyping

    PMID:34468315

    Open questions at the time
    • Direct promoter occupancy detail limited
    • Single-lab mechanism
  16. 2022 High

    Resolved atomic-resolution Y1/Y2/Y4–NPY/PP–Gi1 structures, revealing subtype-specific binding poses and confirming the conserved aspartate binding determinant.

    Evidence Cryo-EM/X-ray crystallography with receptor mutagenesis and functional assays

    PMID:35507650

    Open questions at the time
    • Y5 receptor structure not resolved
    • Conformational basis of biased signaling not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NPY release dynamics, receptor subtype switching, and tissue-specific Gi effectors are integrated to produce the divergent feeding, autonomic, behavioral, and proliferative outcomes remains unresolved.
  • No unified model linking subtype selection to physiological context
  • Y3/y5 receptor roles incompletely defined
  • Transcriptional control of NPY across tissues only partly mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-162582 Signal Transduction 3
Partners
GNAI1NPY1RNPY2RNPY4RNPY5R

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2022 Cryo-EM/X-ray structures of human Y1, Y2, and Y4 receptors in complex with NPY or pancreatic polypeptide and Gi1 protein reveal distinct binding poses of the peptide ligand across receptor subtypes; the N-terminus of NPY forms extensive interactions with Y1 but not Y2 or Y4 receptors. A conserved aspartate in the third extracellular loop is essential for ligand binding in all four Y receptors but engages different arginine residues on the ligand depending on receptor subtype. Mutagenesis and functional studies confirmed subtype-specific receptor–peptide interactions. Cryo-EM/X-ray crystallography, receptor mutagenesis, functional assays Science advances High 35507650
2015 NPY Y1 receptor (Y1R) activation in the bed nucleus of the stria terminalis (BNST) suppresses binge alcohol drinking by enhancing inhibitory synaptic transmission specifically onto CRF neurons via a Gi-mediated, PKA-dependent postsynaptic mechanism. Chronic alcohol drinking leads to persistent alterations in Y1R function in this circuit in both mice and monkeys. Whole-cell patch-clamp electrophysiology, pharmacological receptor agonist/antagonist application, chemogenetics (DREADD), convergent physiological and behavioral assays Nature neuroscience High 25751534
2019 NPY, but not AgRP or GABA, is uniquely required for the long-lasting (sustained) hunger drive generated by AgRP neuron stimulation. Selective deletion of NPY from AgRP neurons abolished optically-stimulated feeding; re-expression of NPY specifically in AgRP neurons rescued this phenotype. Conditional knockout (cell-type-specific NPY deletion), optogenetics, re-expression rescue experiment eLife High 31033437
2000 NPY potentiates phenylephrine-induced MAPK (ERK, JNK, p38) activation and PKC stimulation in primary neonatal cardiomyocytes via NPY Y5 receptors coupled to Gi protein in a pertussis-toxin-sensitive, calcium-independent manner; this synergism is specific to alpha-adrenergic (phenylephrine) but not angiotensin II stimulation. Neonatal cardiomyocyte culture, pharmacological agonist/antagonist studies, pertussis toxin treatment, Western blot (MAPK phosphorylation), PKC activity assay Proceedings of the National Academy of Sciences of the United States of America High 10660688
1993 NPY-2 (Y2) receptor agonist NPY(13-36) and NPY-1 (Y1) agonist [Pro34]-NPY have opposite effects on high-threshold calcium currents in rat nodose ganglion neurons: Y2 activation decreases and Y1 activation increases peak transient high-threshold Ca2+ current amplitude. Whole-cell patch-clamp electrophysiology with selective receptor agonists Journal of neurophysiology High 8395583
2001 NPY produced by human adrenal chromaffin cells locally enhances catecholamine secretion in an autocrine/paracrine manner, likely through the putative y3 receptor; Y1, Y2, Y4, and Y5 receptor mRNAs are expressed and functional (stimulate intracellular calcium rise) on chromaffin cells, but an NPY-immunoneutralizing antibody (not receptor-selective antagonists) markedly attenuated constitutive catecholamine release. RT-PCR, receptor-selective agonist/antagonist pharmacology, intracellular calcium measurement, immunoneutralization, RIA for catecholamines and NPY The Journal of clinical endocrinology and metabolism Medium 11739470
2016 NPY promotes intestinal epithelial cell proliferation and suppresses apoptosis through PI3-K/pAkt (β-catenin) signaling and downregulation of miR-375; NPY knockout mice show reduced polyp formation in a DSS-induced colitis-tumorigenesis model. NPY knockout mouse model (in vivo), intestinal epithelial cell line (T84) in vitro, Western blot, PCNA/Ki67/TUNEL staining, miRNA expression analysis American journal of physiology. Gastrointestinal and liver physiology Medium 27856419
2010 ATP-induced neuroproliferation in adult mouse olfactory epithelium requires NPY upregulation followed by Y1 receptor activation; intranasal purinergic receptor antagonism blocks NPY upregulation, and Y1 receptor antagonism blocks BrdU incorporation (proliferation). Intranasal pharmacological interventions, BrdU labeling, protein quantification (Western blot/IHC), purinergic receptor antagonist pre-treatment Neurobiology of disease Medium 20211262
2008 NPY elicits an attractive axon turning response in embryonic DRG growth cones and increases growth rate via the NPY Y1 receptor; Y1 receptor is expressed in neuroblasts of the rostral migratory stream; Y1- or Y2-receptor knockout mice have fewer proliferating precursor cells and neuroblasts in the subventricular zone/rostral migratory stream and fewer olfactory bulb neurons. Growth cone turning assay (live imaging, asymmetric gradient application), knockout mouse analysis, immunohistochemistry Nutrition (Burbank, Los Angeles County, Calif.) Medium 18725084
2008 NPY receptor binding requires a conserved aspartate residue in the third extracellular loop of all four Y receptors; the specific arginine on the NPY ligand that interacts with this aspartate differs depending on receptor subtype. These were determined by receptor mutagenesis, chimeric receptors, and modified peptide synthesis. Receptor mutagenesis, receptor chimeras, peptide analog synthesis, binding assays Nutrition (Burbank, Los Angeles County, Calif.) Medium 18725084
2000 Human adipocytes predominantly express Y1 receptors (high-affinity sites for [125I]PYY and [125I](Leu31,Pro34)PYY with Y1 pharmacological profile) that mediate NPY's antilipolytic effect and stimulate leptin secretion; Y2 receptor expression is absent. Both effects were fully blocked by selective Y1 antagonists SR120819A and BIBP3226. RT-PCR, radioligand binding assay, [35S]GTPγS binding, lipolysis assay in isolated adipocytes, leptin secretion RIA, receptor antagonists FEBS letters Medium 10858507
1997 In the dorsal vagal complex (DVC), Y2 receptor activation suppresses TRH-stimulated gastric motility (mimicking peripheral PYY action), while Y1 receptor activation stimulates gastric motility from basal state; NPY effects depend on the motility state. PYY is rapidly converted to a Y2-selective agonist by DPP-IV (dipeptidyl aminopeptidase IV), explaining its predominant Y2 action in this context. Microinjection of receptor-selective agonists into DVC, in vivo gastric motility measurement Neurogastroenterology and motility Medium 9198086
1993 Microinjection of Y1 receptor agonist [Leu31,Pro34]NPY into the nucleus tractus solitarius (NTS) produces vasodepressor and bradycardic responses; sub-picomolar doses of the Y2 agonist NPY(13-36) into NTS counteract these Y1-mediated vasodepressor responses, indicating a Y2/Y1 receptor-receptor interaction in the NTS. Stereotaxic microinjection of receptor-selective agonists, in vivo blood pressure and heart rate measurement Brain research Medium 8221064
2001 NPY, acting through Y1 receptor (postsynaptic), potentiates phenylephrine (alpha1-adrenergic)-induced vasopressin and oxytocin release from hypothalamo-neurohypophysial explants in a sustained manner; Y1 agonist [Leu31,Pro34]-NPY increases VP and OT release but does not potentiate ATP-induced responses, indicating signaling specificity. Perifusion of hypothalamic-neurohypophysial explants, selective receptor agonists, RIA for vasopressin and oxytocin American journal of physiology. Regulatory, integrative and comparative physiology Medium 11124136
2015 In the central amygdala (CEm), NPY Y2 receptors are located presynaptically (not on NPY neurons themselves) and their activation by Y2 agonist PYY3-36 reduces both inhibitory and excitatory synaptic transmission. Absence of NPY or Y2 receptors leads to increased GABA release specifically at inhibitory synapses in the CEm. Retrograde tract tracing, immunofluorescence, whole-cell patch-clamp electrophysiology, Y2 receptor knockout mice Brain structure & function Medium 26365505
2002 NPY antidepressant-like activity in the mouse forced swimming test is mediated by the Y1 receptor subtype: Y1 agonist [Leu31Pro34]PYY mimics NPY's anti-immobility effect, Y1 antagonists (BIBO3304, BIBP3226) block it, while Y2 agonist NPY(13-36) is inactive and Y2 antagonist BIIE0246 also reduces immobility (presumably by potentiating endogenous NPY release). Intracerebroventricular injection, mouse forced swimming test, receptor-selective agonists and antagonists, open field locomotion control Neuropsychopharmacology Medium 11927186
1999 NPY Y5 receptor activation mediates NPY-induced feeding and also contributes to decreases in brown adipose tissue temperature and energy expenditure (reduced oxygen consumption); Y1, Y2, and Y4 receptor agonists did not replicate these effects when given ICV. ICV injection of receptor-selective agonists, indirect calorimetry, implanted BAT temperature transponders, food intake measurement The American journal of physiology Medium 10564216
2016 Systemic NPY reduces trigeminocervical complex (TCC) neuronal firing in response to dural nociceptive trigeminovascular activation via the NPY Y1 receptor; Y1 agonist mimics this effect and Y1 antagonist blocks it; Y2 and Y5 receptor agonists are ineffective. In vivo electrophysiology in anesthetized rats, systemic drug administration, receptor-selective agonists/antagonist Pain Medium 27023421
2007 NPY Y1 receptor antagonist (1229U91) blocks NPY-induced torpor-like hypothermia in cold-acclimated Siberian hamsters, whereas Y5 receptor antagonist (CGP71683) does not; Y1 agonist but not Y5 agonist recapitulates the torpor effect, establishing Y1 receptor as necessary and sufficient for NPY-induced torpor. ICV injection, receptor-selective agonists/antagonists, body temperature telemetry, counterbalanced pharmacological design American journal of physiology. Regulatory, integrative and comparative physiology Medium 17989140
2003 NPY suppresses experimental autoimmune encephalomyelitis (EAE) via Y1 receptors: Y1 receptor agonists inhibit EAE induction, a Y1 antagonist causes earlier EAE onset, and ex vivo analysis shows Y1 signaling in autoreactive T cells shifts them toward Th2 and inhibits Th1 responses. Y5 agonist had no protective effect. EAE induction in C57BL/6 mice, pharmacological receptor agonist/antagonist treatment, ex vivo T cell restimulation, cytokine profiling Journal of immunology Medium 14500640
2021 Ascending skeletal interoceptive signaling downregulates hypothalamic NPY expression by inducing SMILE (small heterodimer partner-interacting leucine zipper protein), which binds to pCREB as a transcriptional heterodimer on Npy promoters to inhibit NPY transcription. Reduced NPY signaling (via Y1R inhibition) accelerates free fatty acid oxidation in osteoblasts and rescues bone loss. EP4 sensory nerve knockout mice, hypothalamic molecular analysis, promoter binding (pCREB/SMILE complex), Y1R pharmacological inhibition, bone phenotype analysis eLife Medium 34468315
1985 NPY-like immunoreactivity is transported axonally in peripheral sympathetic neurons at a rapid rate (~3 mm/h), as demonstrated by accumulation above sciatic nerve ligations; reserpine depletes NPY from cardiac sympathetic nerve terminals (but not ganglia) in a manner dependent on intact nerve activity, distinguishing NPY storage/release from noradrenaline; 6-OHDA denervation depletes NPY from terminal fields but increases it in ganglia. Sciatic nerve ligation, reserpine and 6-OHDA pharmacology, radioimmunoassay, immunohistochemistry, HPLC Naunyn-Schmiedeberg's archives of pharmacology Medium 2858824
1990 NPY is co-stored with noradrenaline in large dense-cored vesicles and is released preferentially at high stimulation frequencies or strong sympathetic activation; NPY release is inhibited by prejunctional alpha-2 adrenoceptors and adenosine receptors, and facilitated by angiotensin II or beta-receptor activation. NPY acts prejunctionally to inhibit both NA and NPY release, and postjunctionally to potentiate vasoconstriction. A large amidated C-terminal portion of NPY is necessary for receptor binding, cAMP inhibition, and vasoconstrictor effects. Sympathetic nerve stimulation (peripheral vascular preparations), pharmacological pre/postjunctional dissection, RIA, cAMP assay, denervation supersensitivity experiments Fundamental & clinical pharmacology Medium 2170253
2008 NPY Y2 receptor activation (by NPY(13-36)) provides neuroprotection against AMPA-induced excitotoxicity in hippocampal slice cultures; endogenous NPY via Y1 receptors also contributes to neuroprotection in CA1; AMPA-induced injury increases BDNF in microglia, but this BDNF is not required for the Y2-mediated NPY neuroprotective effect. Organotypic hippocampal slice culture, AMPA excitotoxicity model, propidium iodide uptake, receptor-selective agonists/antagonists, TrkB-Fc and neutralizing antibody blockade, ELISA, immunohistochemistry The European journal of neuroscience Medium 18412629
2002 Y1 receptor immunoreactivity is present in axonal processes of DRG neurons with centrifugal (peripheral) transport demonstrated by accumulation proximal to sciatic nerve crush lesions; Y1R co-localizes with CGRP in peripheral sensory axons and nerve endings near the epidermis. Immunohistochemistry, nerve crush/ligation lesion experiments, double-labeling (Y1R + CGRP), dorsal rhizotomy Experimental neurology Medium 11869028
2014 NPY acting through Y1 receptors induces vasoconstriction and proliferation of pulmonary arterial smooth muscle cells via p38 and PKD pathway activation; selective Y1 antagonist BIBO 3304 blocks both effects; Y1 receptor expression is upregulated in pulmonary hypertension tissue. Wire myography, calcium imaging, Western blot (p38/PKD phosphorylation), thymidine incorporation proliferation assay, quantitative PCR, selective Y1 antagonist British journal of pharmacology Medium 24779394
2017 Insulin signaling specifically in NPY neurons controls food intake, energy expenditure, and GH/IGF-1 axis; selective deletion of the insulin receptor in NPY neurons (in both flies and mice) leads to increased energy stores, obesity, and impaired insulin sensitivity. Cell-type-specific conditional knockout of insulin receptor in NPY neurons (Drosophila and mouse), metabolic phenotyping Molecular metabolism Medium 28580287

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 The NPY system in stress, anxiety and depression. Neuropeptides 479 15337373
2008 Genetic variation in human NPY expression affects stress response and emotion. Nature 333 18385673
2004 NPY and Y receptors: lessons from transgenic and knockout models. Neuropeptides 229 15337371
2010 Therapeutic potential of neuropeptide Y (NPY) receptor ligands. EMBO molecular medicine 214 20972986
2009 Classification of NPY-expressing neocortical interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 196 19295167
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 171 10715359
2004 Molecular evolution of NPY receptor subtypes. Neuropeptides 170 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
2015 NPY signaling inhibits extended amygdala CRF neurons to suppress binge alcohol drinking. Nature neuroscience 164 25751534
1996 Expression of leptin receptor mRNA in the hypothalamic arcuate nucleus--relationship with NPY neurones. Neuroreport 145 9116246
2004 Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides 138 15337374
2015 The role of NPY in learning and memory. Neuropeptides 134 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
1988 NPY and related substances. Critical reviews in neurobiology 125 2848631
2017 Insulin controls food intake and energy balance via NPY neurons. Molecular metabolism 123 28580287
2006 Physiology and gene regulation of the brain NPY Y1 receptor. Frontiers in neuroendocrinology 122 16989896
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 114 27461050
1990 Pharmacology of noradrenaline and neuropeptide tyrosine (NPY)-mediated sympathetic cotransmission. Fundamental & clinical pharmacology 109 2170253
2019 Sustained NPY signaling enables AgRP neurons to drive feeding. eLife 108 31033437
2007 NPY and receptors in immune and inflammatory diseases. Current topics in medicinal chemistry 98 17979783
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
2007 NPY receptors in human cancer: a review of current knowledge. Peptides 92 17223228
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 91 19854625
2002 Brain neuropeptide Y (NPY) in stress and alcohol dependence. Reviews in the neurosciences 91 12013027
2006 Cloning and characterization of neuropeptide Y (NPY) and cocaine and amphetamine regulated transcript (CART) in Atlantic cod (Gadus morhua). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 83 17254820
1992 The murine NPY-1 receptor gene. Structure and delineation of tissue-specific expression. FEBS letters 83 1468559
2016 Sucralose Promotes Food Intake through NPY and a Neuronal Fasting Response. Cell metabolism 82 27411010
2003 Neuropeptide Y (NPY) suppresses experimental autoimmune encephalomyelitis: NPY1 receptor-specific inhibition of autoreactive Th1 responses in vivo. Journal of immunology (Baltimore, Md. : 1950) 82 14500640
2000 Neuropeptide Y (NPY) potentiates phenylephrine-induced mitogen-activated protein kinase activation in primary cardiomyocytes via NPY Y5 receptors. Proceedings of the National Academy of Sciences of the United States of America 80 10660688
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 NPY regulation of bone remodelling. Neuropeptides 70 19748118
1998 NPY and food intake: discrepancies in the model. Regulatory peptides 68 9802436
2009 Neuropeptide Y (NPY) suppresses yohimbine-induced reinstatement of alcohol seeking. Psychopharmacology 67 20012021
2006 Spinal mechanisms of NPY analgesia. Peptides 67 17194506
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
2001 NPY regulates catecholamine secretion from human adrenal chromaffin cells. The Journal of clinical endocrinology and metabolism 64 11739470
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
1994 The appearance of NPY and VIP in sympathetic neuroblasts and subsequent alterations in their expression. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 8027792
2017 The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders. International review of neurobiology 60 29056151
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
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
2002 NPY Y1 receptors are present in axonal processes of DRG neurons. Experimental neurology 56 11869028
1995 Hypothalamic NPY and prepro-NPY mRNA in Djungarian hamsters: effects of food deprivation and photoperiod. The American journal of physiology 56 7503297
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
1992 Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) levels are elevated in plasma and decreased in vena cava during endotoxin shock in the rat. Circulatory shock 53 1551183
2015 Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala. Brain structure & function 52 26365505
2009 Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond. Alcohol (Fayetteville, N.Y.) 52 19913192
2007 NPY and pain as seen from the histochemical side. Peptides 51 17234301
2004 Importance of NPY Y1 receptor-mediated pathways: assessment using NPY Y1 receptor knockouts. Neuropeptides 50 15337379
1997 Developmental expression of NPY, PYY and PP in the rat pancreas and their coexistence with islet hormones. Regulatory peptides 50 9100283
2015 Neuropeptide Y (NPY) in tumor growth and progression: Lessons learned from pediatric oncology. Neuropeptides 49 26549645
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
2010 NPY mediates ATP-induced neuroproliferation in adult mouse olfactory epithelium. Neurobiology of disease 45 20211262
2010 Hypothalamic expression of porcine leptin receptor (LEPR), neuropeptide Y (NPY), and cocaine- and amphetamine-regulated transcript (CART) genes is influenced by LEPR genotype. Mammalian genome : official journal of the International Mammalian Genome Society 45 21128076
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
2021 NPY and Gene Therapy for Epilepsy: How, When,... and Y. Frontiers in molecular neuroscience 44 33551745
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
1993 Agonists for neuropeptide Y receptor subtypes NPY-1 and NPY-2 have opposite actions on rat nodose neuron calcium currents. Journal of neurophysiology 43 8395583
2012 NPY and NPY receptors in airway structural and inflammatory cells in allergic asthma. Experimental and molecular pathology 41 22705097
2010 Central administration of NPY or an NPY-Y5 selective agonist increase in vivo extracellular monoamine levels in mesocorticolimbic projecting areas. Neuropharmacology 41 20868698
2021 Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY. eLife 40 34468315
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
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
1993 Microinjections of subpicomolar amounts of NPY(13-36) into the nucleus tractus solitarius of the rat counteract the vasodepressor responses of NPY(1-36) and of a NPY Y1 receptor agonist. Brain research 36 8221064
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
2007 NPY and NPY receptors in vascular remodeling. Current topics in medicinal chemistry 33 17979779
2001 Substance P and NPY differentially potentiate ATP and adrenergic stimulated vasopressin and oxytocin release. American journal of physiology. Regulatory, integrative and comparative physiology 33 11124136
1998 NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression: potential roles of plasma insulin and leptin. Regulatory peptides 33 9802439
2012 Neuropeptide Y (NPY) in the extended amygdala is recruited during the transition to alcohol dependence. Neuropeptides 32 22938859
2008 Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. Neuropeptides 31 18468678
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
2017 NPY and CGRP Inhibitor Influence on ERK Pathway and Macrophage Aggregation during Fracture Healing. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 28315869
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

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