Affinage

TAC3

Tachykinin-3 · UniProt Q9UHF0

Length
121 aa
Mass
13.4 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAC3 encodes neurokinin B (NKB), a tachykinin neuropeptide that signals through the NK3 receptor (TACR3/NK3R) to regulate diverse neuroendocrine and peripheral functions. In the hypothalamus, NKB operates as an autocrine/paracrine signal within arcuate KNDy (kisspeptin/NKB/dynorphin) neurons to drive pulsatile GnRH secretion, and loss-of-function mutations in TAC3 cause normosmic congenital hypogonadotropic hypogonadism in humans (PMID:20194706, PMID:21914775). Beyond reproduction, NKB/NK3R signaling directly stimulates dopamine release from mesencephalic neurons, enhances noradrenergic transmission in the locus coeruleus, promotes vasopressin release from hypothalamic paraventricular nucleus neurons, mediates fear memory consolidation in the centromedial amygdala, and induces nitric oxide-dependent smooth muscle relaxation in gut and vasculature (PMID:9081631, PMID:8865192, PMID:1281741, PMID:24976214, PMID:7531357, PMID:8680725). TAC3 transcription is directly regulated by NRSF/REST binding to its promoter (PMID:19539370).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1992 Medium

    Early work established that NKB's receptor NK3R is functionally active in the hypothalamic PVN, where it triggers vasopressin-dependent cardiovascular responses, revealing a central neuroendocrine role for the TAC3/NK3R axis beyond classical peripheral tachykinin functions.

    Evidence Stereotaxic senktide microinjection into rat PVN with blood pressure recording and V1 receptor antagonist blockade

    PMID:1281741

    Open questions at the time
    • Single lab; vasopressin release was inferred from V1 antagonist blockade rather than measured directly
    • Endogenous NKB involvement not demonstrated (only exogenous agonist)
    • Downstream intracellular signaling not characterized
  2. 1993 High

    Chimeric NK1/NK3 receptor studies defined the molecular determinants of NKB binding selectivity, showing that carboxyl-terminal transmembrane domains are critical for NKB recognition while transmembrane segments III–IV govern senktide selectivity, providing the first structural framework for how NK3R distinguishes NKB from other tachykinins.

    Evidence Chimeric receptor construction with stable transfection and competition radioligand binding

    PMID:7681831 PMID:8117303

    Open questions at the time
    • No crystal structure or cryo-EM confirmation of binding poses
    • Species-selective residues mapped but broader structure–function of full-length receptor unknown
  3. 1994 High

    NK3R activation was shown to mediate nitric oxide-dependent NANC relaxation in gut smooth muscle and endothelium-dependent vasorelaxation in mesenteric artery, establishing NKB/NK3R as a peripheral regulator of smooth muscle tone through an NO signaling pathway.

    Evidence Isolated organ bath pharmacology with NO synthase inhibitors, endothelium removal, and selective NK3R antagonists in guinea-pig colon and rat mesenteric artery

    PMID:7531357 PMID:8680725

    Open questions at the time
    • Source of endogenous NKB in these tissues not identified
    • In vivo relevance of NKB-mediated vasodilation not demonstrated
  4. 1996 High

    NKB/NK3R signaling was demonstrated to directly stimulate dopamine release and intracellular Ca²⁺ elevation in mesencephalic dopamine neurons, and to enhance noradrenergic and cholinergic transmission in vivo, revealing NKB as a modulator of multiple monoaminergic and cholinergic systems.

    Evidence Primary mesencephalic cultures with [³H]DA release and Ca²⁺ imaging; in vivo microdialysis in guinea-pig locus coeruleus, substantia nigra, VTA, and septal area with senktide and stereoselective NK3R antagonists

    PMID:8865192 PMID:9081631 PMID:9845011

    Open questions at the time
    • Circuit-level connectivity between NKB-expressing neurons and dopaminergic/noradrenergic targets not mapped
    • Physiological conditions that trigger endogenous NKB release onto these neurons remain unclear
  5. 1998 High

    A zinc-binding site in NK3R transmembrane segment V was identified as a positive allosteric modulator of NKB binding and signaling, revealing an endogenous modulatory mechanism for NK3R pharmacology.

    Evidence Site-directed mutagenesis of HisV:01 with radioligand binding and functional assays in the presence of ZnCl₂

    PMID:9849872

    Open questions at the time
    • Physiological relevance of zinc modulation at synaptic concentrations not established
    • No structural confirmation of the zinc coordination geometry
  6. 2005 Medium

    NK3R activation on hypothalamic PVN vasopressin neurons was shown to trigger receptor internalization in vivo, providing a cellular mechanism for signal termination and confirming that NKB/NK3R drives vasopressin secretion through direct action on VP neurons.

    Evidence In vivo stereotaxic injection with immunohistochemical tracking of NK3R subcellular redistribution and VP radioimmunoassay

    PMID:16357093

    Open questions at the time
    • Single lab observation
    • Kinetics and recycling pathway of internalized NK3R on VP neurons not characterized
    • Contribution of endogenous NKB versus pharmacological agonist dosing unclear
  7. 2008 High

    In a Parkinson's disease model, chronic L-DOPA upregulated striatal NKB expression, and NK3R activation stimulated dopamine release via CaMKII/tyrosine hydroxylase phosphorylation, while NK3R blockade enhanced L-DOPA behavioral effects — positioning NKB/NK3R as a feedback inhibitor of dopaminergic signaling relevant to L-DOPA therapy.

    Evidence 6-OHDA rat model with in situ hybridization, amperometry in striatal slices, phosphoprotein immunoblotting, and behavioral rotometry

    PMID:18423776

    Open questions at the time
    • Mechanism of NKB upregulation by L-DOPA not defined
    • Translational relevance to human PD not tested
  8. 2009 High

    NRSF/REST was identified as a direct transcriptional regulator of TAC3, with ChIP confirming binding to the NKB promoter and carbamazepine reducing NRSF-driven TAC3 induction, establishing a transcriptional control mechanism for NKB expression.

    Evidence Chromatin immunoprecipitation, reporter gene assays, and RT-PCR of endogenous TAC3

    PMID:19539370

    Open questions at the time
    • Physiological signals that modulate NRSF occupancy at TAC3 promoter in neurons not identified
    • Whether sNRSF isoform has distinct regulatory effects in vivo is unknown
  9. 2010 High

    Human genetic evidence established that TAC3 loss-of-function mutations cause normosmic congenital hypogonadotropic hypogonadism by impairing hypothalamic GnRH pulse generation, placing NKB as essential for reproductive neuroendocrine function.

    Evidence Homozygous TAC3 splice-site mutations in CHH kindreds; hormonal profiling and pulsatile GnRH rescue of LH secretion and fertility

    PMID:20194706 PMID:22031817

    Open questions at the time
    • Genotype–phenotype variability (some patients show partial reversal) not mechanistically explained
    • Whether heterozygous carriers have subtle reproductive phenotypes is unclear
  10. 2011 High

    The KNDy neuron model was experimentally validated: NKB is coexpressed with kisspeptin and dynorphin in arcuate neurons, and NK3R agonism directly activates KNDy neurons but not GnRH neurons, establishing NKB as an auto-feedback signal that shapes pulsatile kisspeptin/GnRH output.

    Evidence In situ hybridization for mRNA colocalization, electrophysiology of KNDy vs. GnRH neurons in mouse brain slices, LH secretion assays

    PMID:21914775

    Open questions at the time
    • Relative contributions of NKB versus dynorphin in setting pulse frequency not quantified
    • Whether NKB acts solely in autocrine mode or also on neighboring KNDy neurons is unresolved
  11. 2014 High

    NKB/NK3R signaling was shown to be necessary and sufficient for fear memory consolidation in the centromedial amygdala, extending TAC3 function beyond neuroendocrine regulation to emotional memory circuits.

    Evidence Lentiviral Tac2 overexpression, DREADD-based chemogenetic silencing, NK3R antagonist osanetant, and fear conditioning behavioral assays in mice

    PMID:24976214

    Open questions at the time
    • Downstream molecular targets of NK3R in CeM fear circuits not identified
    • Relevance to human PTSD or anxiety disorders not tested
  12. 2018 High

    NKB/NK3R signaling in the medial amygdala was found to drive LH release through a kisspeptin-independent pathway, revealing a second, extrahypothalamic reproductive circuit distinct from the canonical arcuate KNDy mechanism.

    Evidence Cell-type-specific DREADD activation, NK3R agonist stereotaxic injection, LH measurement, and Kiss1r knockout comparison in mice

    PMID:30565563

    Open questions at the time
    • Identity of the downstream relay neurons from MePD to GnRH neurons is unknown
    • Physiological conditions that engage the MePD NKB pathway versus the arcuate KNDy pathway are not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how NKB pulse dynamics are translated into GnRH pulse frequency at the molecular level, the identity of downstream effectors mediating NK3R actions in fear and dopaminergic circuits, and the physiological significance of peripheral NKB/NK3R signaling (ovarian, vascular) in humans.
  • No integrated model connecting NKB pulse generation, kisspeptin release, and GnRH neuron activation at single-cell resolution
  • Structural basis of NKB–NK3R interaction remains without cryo-EM or crystal structure
  • Relative contributions of autocrine vs. paracrine NKB signaling within KNDy network are not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-112316 Neuronal System 5 R-HSA-1266738 Developmental Biology 4
Partners
KISS1PDYNRESTTACR3

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 Loss-of-function mutations in TAC3 (neurokinin B gene) cause normosmic congenital hypogonadotropic hypogonadism (CHH) in humans by impairing hypothalamic GnRH pulsatile release; pulsatile GnRH administration restored LH secretion and fertility, establishing the hypothalamic origin of the gonadotropin deficiency. Human genetics (homozygous splice-site mutations in TAC3 identified in CHH patients), hormonal profiling, pulsatile GnRH challenge The Journal of clinical endocrinology and metabolism High 20194706
2011 TAC3 mutations (splice-site deletion of neurokinin B) and TACR3 mutations produce a distinct neuroendocrine profile characterized by low GnRH pulsatile frequency, low-frequency alpha-subunit pulses, and an elevated FSH/LH ratio; pulsatile GnRH corrected these deficits, confirming that NKB acts upstream of the pituitary at the hypothalamic level. Cohort sequencing, functional modeling of missense mutant NK3R (Tyr267Asn misfolding), LH pulse profiling, pulsatile GnRH challenge PloS one High 22031817
2011 In the male mouse arcuate nucleus, NKB (encoded by Tac2, the rodent ortholog) is coexpressed with kisspeptin and dynorphin in KNDy neurons; senktide (NK3R agonist) activates KNDy neurons (which express Tacr3) but has no direct effect on GnRH neurons, establishing NKB as an auto-feedback signal within KNDy neurons to generate pulsatile kisspeptin/GnRH secretion. In situ hybridization for mRNA coexpression, electrophysiology (senktide stimulation of KNDy vs GnRH neurons), LH secretion assays Endocrinology High 21914775
2014 The Tac2 gene product NKB, acting through the NK3 receptor (Nk3R), is required for fear memory consolidation in the centromedial amygdala (CeM); Tac2 is colocalized with GAD65 and CaMKIIα neurons in CeM, lentiviral Tac2 overexpression enhances fear consolidation, and this effect is blocked by the NK3R antagonist osanetant. Lentiviral overexpression, DREADDs-based chemogenetic silencing, NK3R antagonist (osanetant) blockade, fear conditioning behavioral assays, immunofluorescence colocalization Neuron High 24976214
2009 The human TAC3 gene promoter is directly bound and regulated by Neuron Restrictive Silencing Factor (NRSF/REST) and its truncated isoform sNRSF, leading to increased TAC3 expression; chromatin immunoprecipitation (ChIP) confirmed direct NRSF binding to the NKB promoter in vivo, and the anticonvulsant carbamazepine diminished this induction. ChIP (chromatin immunoprecipitation), reporter gene assay, RT-PCR of endogenous TAC3 expression Neuropeptides High 19539370
2018 NKB/NK3R signaling in the posterodorsal medial amygdala (MePD) induces LH release in a kisspeptin-independent manner; chemogenetic (DREADD) activation of MePD Kiss1 neurons also induces LH release, but NKB stimulation of LH in the MePD is independent of Kiss1 neurons, demonstrating two distinct neuronal circuits in the MePD regulating reproductive function. Chemogenetic (DREADD) activation of cell-type-specific neuronal populations, NK3R agonist stereotaxic injection, LH measurement, genetic Kiss1r knockout comparison eLife High 30565563
2012 In zebrafish (Danio rerio), TAC3 encodes two precursors (TAC3a and TAC3b) producing four NKB-like peptides; transcription reporter assays in eukaryotic cells showed that these NKB peptides activate TACR3 downstream signaling, establishing functional conservation of the TAC3/TACR3 system in teleosts. cDNA cloning, genomic synteny/phylogenetic analysis, transcription reporter assays in cultured cells Molecular and cellular endocrinology Medium 22580006
2014 In carp pituitary cells, NKB (TAC3 product) stimulates prolactin (PRL) and somatolactin-α (SLα) secretion and gene expression via NK2 and NK3 receptors respectively, through adenylate cyclase/cAMP/PKA, phospholipase C/IP3/PKC, and Ca2+/CaM/CaMKII signaling cascades, without affecting LH. Primary pituitary cell culture, receptor-selective agonist/antagonist treatments, signaling pathway inhibitors, mRNA/protein expression assays Endocrinology Medium 24971612
1993 Chimeric NK1/NK3 receptor studies identified that multiple transmembrane domains contribute to tachykinin peptide binding selectivity; neurokinin B (NK3 preferred ligand) binding is most sensitive to exchange of the carboxyl-terminal transmembrane segments, while the NK3-selective agonist senktide requires transmembrane segments III and IV from the NK3 receptor. Chimeric receptor construction, stable transfection, competition binding studies The Journal of biological chemistry High 7681831
1994 Species-selective binding of SR 48968 to human vs. rat NK3 receptor was mapped to two residues in the second transmembrane segment (Met134 and Ala146 in human); human/rat chimeric NK3 receptors and single point mutants (V121M and G133A in rat) confirmed these residues collectively account for the species difference in affinity. Chimeric receptor construction, point mutagenesis, radioligand binding in transfected CHO cells Biochemical and biophysical research communications High 8117303
1998 A naturally occurring bis-His zinc-binding site in transmembrane segment V (positions V:01 and V:05) of the NK3A receptor has a positive modulatory effect on neurokinin B binding and function; Zn2+ enhanced [MePhe7]NKB binding to ~150% and potentiated NKB signaling, an effect abolished by Ala-substitution of HisV:01. Site-directed mutagenesis (Ala substitution of HisV:01), radioligand binding, functional assays with ZnCl2 FEBS letters High 9849872
1998 NK3R stimulation in the guinea-pig locus coeruleus increases firing rate of noradrenergic neurons; in vivo microdialysis confirmed that NK3R activation (senktide) increases norepinephrine release in the medial prefrontal cortex, effects blocked by SR 142801 but not its inactive enantiomer SR 142806. Electrophysiology (slice recording), in vivo microdialysis, behavioral assays, pharmacological antagonism Neuroscience High 8865192
1998 NK3R activation (senktide) in the guinea-pig substantia nigra and ventral tegmental area markedly enhances dopamine release in striatum, nucleus accumbens, and prefrontal cortex; NK3R activation in the septal area enhances acetylcholine release in hippocampus; both effects are dose-dependently blocked by SR142801 but not its inactive enantiomer. In vivo microdialysis with selective NK3R agonist (senktide) and antagonist (SR142801), regional brain stereotaxic injection Neuropeptides High 9845011
1994 NK3R stimulation by senktide in guinea-pig colon circular muscle produces NANC relaxation and membrane hyperpolarization primarily through nitric oxide release, as demonstrated by complete blockade with the NO synthase inhibitor L-NOARG (reversed by L-arginine); this effect is tetrodotoxin-sensitive and omega-conotoxin-insensitive, indicating neuronal NK3R-mediated NO release not requiring N-type Ca2+ channels. Isolated organ bath pharmacology, electrophysiology (sucrose gap), pharmacological dissection with L-NOARG, tetrodotoxin, omega-conotoxin Regulatory peptides High 7531357
1995 In rat mesenteric artery, NK3R activation (senktide) produces endothelium-dependent vasorelaxation mediated by nitric oxide; this was blocked by L-NOARG (NO synthase inhibitor) and by SR 142801 (selective NK3R antagonist) but not by NK1 or NK2 antagonists. Isolated vessel pharmacology, endothelium removal, NO synthase inhibition, selective receptor antagonists British journal of pharmacology High 8680725
1996 NK3R activation by senktide in mesencephalic dopamine neuron cultures increases spontaneous [3H]dopamine release and intracellular Ca2+ in a Ca2+-dependent, tetrodotoxin-resistant (direct) manner; effects blocked by NK3R antagonist SR142801 but not NK1 or NK2 antagonists, and pre-treatment with the DA neurotoxin MPP+ abolished senktide-responsive Ca2+ elevations, confirming the response is in DA neurons. Primary mesencephalic cell cultures, [3H]DA release assay, fluo-3 Ca2+ imaging, pharmacological dissection, MPP+ neurotoxin pretreatment The European journal of neuroscience High 9081631
2008 Chronic L-DOPA treatment in the 6-OHDA rat model of Parkinson's disease increases striatal NKB expression (TAC3/Tac2 product) in the dopamine-depleted hemisphere; NK3R activation (senktide) increases dopamine release (amperometry) and phosphorylation of tyrosine hydroxylase at Ser19 (CaMKII site) and CaMKII at Thr286 in striatal slices, effects blocked by NK3R antagonist SB222200; combined NK3R antagonism with L-DOPA increases contralateral rotations, indicating NKB/NK3R exerts feedback inhibition on L-DOPA actions. 6-OHDA lesion rat model, in situ hybridization, pharmacological treatments, amperometry, phosphoprotein immunoblotting, behavioral rotometry Neuropharmacology High 18423776
2005 NK3R agonist-induced internalization of the NK3R on vasopressin neurons in the hypothalamic paraventricular nucleus (PVN) was demonstrated in vivo; senktide injection caused translocation of NK3R immunoreactivity from the plasma membrane to cytoplasm (internalization), which was blocked by NK3R antagonist SB-222200 that also blocked senktide-induced vasopressin release; hypertonic saline similarly caused NK3R internalization on VP neurons. In vivo stereotaxic injection, immunohistochemistry to track NK3R subcellular localization, VP radioimmunoassay, NK3R antagonist pretreatment American journal of physiology. Regulatory, integrative and comparative physiology Medium 16357093
2000 NK3R and NK1R in rat myenteric neurons undergo independent, agonist-induced endocytosis: selective NK3R agonist senktide triggers NK3R endocytosis without affecting NK1R, and this is blocked by NK3R antagonist SR-142801 but not NK1R antagonist; monensin (recycling blocker) accumulates NK1R but not NK3R in cytoplasm, indicating different recycling mechanisms for the two receptor subtypes. Immunohistochemistry tracking receptor subcellular distribution, selective agonists/antagonists, pharmacological recycling inhibitor (monensin) Neuroscience Medium 10996469
1992 NK3R (neurokinin B receptor) activation in rat paraventricular nucleus (PVN) increases blood pressure, an effect blocked by vasopressin V1 receptor antagonist, establishing that NK3R stimulation in the PVN triggers vasopressin release from the pituitary to cause pressor responses. Stereotaxic microinjection of senktide into PVN, blood pressure measurement, V1 receptor antagonist pretreatment Brain research Medium 1281741
2011 TACR3 promoter DNA methylation at a specific CpG site is decreased in marmoset monkeys after repeated cocaine administration in a conditioned place preference paradigm, identifying TACR3 as a locus for cocaine-induced epigenetic modification. Bisulfite pyrosequencing of TACR3 promoter CpG sites in brain tissue from conditioned place preference paradigm marmosets Addiction biology Low 22070124
2014 NKB (TAC3 product) and NK3R are expressed and functionally active in human ovarian granulosa cells; kisspeptin increases intracellular Ca2+ in granulosa cells while NKB inhibits kisspeptin-induced Ca2+ mobilization, an effect partially mediated by NK3R and blocked by a cocktail of NK1/NK2/NK3 receptor antagonists. RT-PCR, immunocytochemistry, western blot, intracellular Ca2+ measurement (live imaging), tachykinin receptor antagonist pharmacology Human reproduction Medium 25316443

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 190 21914775
1996 Characterization of antisera specific to NK1, NK2, and NK3 neurokinin receptors and their utilization to localize receptors in the rat gastrointestinal tract. The Journal of neuroscience : the official journal of the Society for Neuroscience 189 8824334
2010 TAC3 and TACR3 defects cause hypothalamic congenital hypogonadotropic hypogonadism in humans. The Journal of clinical endocrinology and metabolism 181 20194706
1995 SR 142801, the first potent non-peptide antagonist of the tachykinin NK3 receptor. Life sciences 169 7830490
1996 Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat. The Journal of comparative neurology 166 8788251
1999 The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription. The Journal of biological chemistry 142 10559189
2009 Sex differences in the regulation of Kiss1/NKB neurons in juvenile mice: implications for the timing of puberty. American journal of physiology. Endocrinology and metabolism 111 19755669
1993 Chimeric NK1 (substance P)/NK3 (neurokinin B) receptors. Identification of domains determining the binding specificity of tachykinin agonists. The Journal of biological chemistry 107 7681831
1998 Activation of dopaminergic and cholinergic neurotransmission by tachykinin NK3 receptor stimulation: an in vivo microdialysis approach in guinea pig. Neuropeptides 97 9845011
2005 Opinion: NK3 receptor antagonists: the next generation of antipsychotics? Nature reviews. Drug discovery 95 16341062
2016 A Novel Tiller Angle Gene, TAC3, together with TAC1 and D2 Largely Determine the Natural Variation of Tiller Angle in Rice Cultivars. PLoS genetics 94 27814357
2014 A role for Tac2, NkB, and Nk3 receptor in normal and dysregulated fear memory consolidation. Neuron 83 24976214
1998 Roles of neuronal NK1 and NK3 receptors in synaptic transmission during motility reflexes in the guinea-pig ileum. British journal of pharmacology 83 9723948
1990 Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes. British journal of pharmacology 82 1694464
2005 Cortical sources of CRF, NKB, and CCK and their effects on pyramidal cells in the neocortex. Cerebral cortex (New York, N.Y. : 1991) 80 16339088
1998 Involvement of tachykinin NK3 receptors in citric acid-induced cough and bronchial responses in guinea pigs. American journal of respiratory and critical care medicine 80 9655705
1997 Localisation of neurokinin 3 (NK3) receptor immunoreactivity in the rat gastrointestinal tract. Cell and tissue research 72 9182595
1992 Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. Proceedings of the National Academy of Sciences of the United States of America 72 1280822
2011 Normosmic congenital hypogonadotropic hypogonadism due to TAC3/TACR3 mutations: characterization of neuroendocrine phenotypes and novel mutations. PloS one 69 22031817
2015 The NK3 Receptor Antagonist ESN364 Interrupts Pulsatile LH Secretion and Moderates Levels of Ovarian Hormones Throughout the Menstrual Cycle. Endocrinology 66 26305889
2004 Neurokinin NK1 and NK3 receptors as targets for drugs to treat gastrointestinal motility disorders and pain. British journal of pharmacology 65 15023866
2015 The NK3 Receptor Antagonist ESN364 Suppresses Sex Hormones in Men and Women. The Journal of clinical endocrinology and metabolism 64 26653113
2001 Localization of NK1 and NK3 receptors in guinea-pig brain. Regulatory peptides 60 11179779
1990 Antagonists for the neurokinin NK-3 receptor evaluated in selective receptor systems. Regulatory peptides 56 2176308
2014 Expression of neurokinin B/NK3 receptor and kisspeptin/KISS1 receptor in human granulosa cells. Human reproduction (Oxford, England) 50 25316443
2003 Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action. Neurogastroenterology and motility 50 12846724
2007 Disruption of the neurokinin-3 receptor (NK3) in mice leads to cognitive deficits. Psychopharmacology 49 17558564
2006 Selective blockade of NK2 or NK3 receptors produces anxiolytic- and antidepressant-like effects in gerbils. Pharmacology, biochemistry, and behavior 46 16624395
2012 The evolution of tachykinin/tachykinin receptor (TAC/TACR) in vertebrates and molecular identification of the TAC3/TACR3 system in zebrafish (Danio rerio). Molecular and cellular endocrinology 41 22580006
1996 Electrophysiological, behavioural and biochemical evidence for activation of brain noradrenergic systems following neurokinin NK3 receptor stimulation. Neuroscience 41 8865192
2019 Environmentally Relevant Perinatal Exposures to Bisphenol A Disrupt Postnatal Kiss1/NKB Neuronal Maturation and Puberty Onset in Female Mice. Environmental health perspectives 40 31652106
2021 Extracellular Vesicles From the Human Natural Killer Cell Line NK3.3 Have Broad and Potent Anti-Tumor Activity. Frontiers in cell and developmental biology 39 34368150
2012 Mutational analysis of TAC3 and TACR3 genes in patients with idiopathic central pubertal disorders. Arquivos brasileiros de endocrinologia e metabologia 39 23329188
2004 Tachykinin NK3-receptor deficiency does not inhibit pulmonary eosinophilia in allergic mice. Pharmacological research 38 15501700
1992 Stable expression of high affinity NK1 (substance P) and NK2 (neurokinin A) receptors but low affinity NK3 (neurokinin B) receptors in transfected CHO cells. FEBS letters 38 1311270
2014 Novel pituitary actions of TAC3 gene products in fish model: receptor specificity and signal transduction for prolactin and somatolactin α regulation by neurokinin B (NKB) and NKB-related peptide in carp pituitary cells. Endocrinology 36 24971612
2007 In vitro and in vivo characterization of the non-peptide NK3 receptor antagonist SB-223412 (talnetant): potential therapeutic utility in the treatment of schizophrenia. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 36 17728699
2000 Localisation of tachykinin NK1 and NK3 receptors in the human prefrontal and visual cortex. Neuroscience letters 35 10754218
2012 Central administration of neurokinin B activates kisspeptin/NKB neurons in the arcuate nucleus and stimulates luteinizing hormone secretion in ewes during the non-breeding season. The Journal of reproduction and development 34 22972185
1997 Potency and selectivity of the tachykinin NK3 receptor antagonist SR 142801. European journal of pharmacology 34 9042606
2003 Role of tachykinin NK1, NK2 and NK3 receptors in the modulation of visceral hypersensitivity in the rat. Neuroscience letters 33 14583381
1998 Natural agonist enhancing bis-His zinc-site in transmembrane segment V of the tachykinin NK3 receptor. FEBS letters 33 9849872
1999 Differential modulation of human immunoglobulin isotype production by the neuropeptides substance P, NKA and NKB. Journal of neuroimmunology 32 10408978
1998 Naloxone-induced changes in tachykinin NK3 receptor modulation of experimental anxiety in mice. Neuroscience letters 31 9885954
1994 Tachykinin NK3 receptor mediates NANC hyperpolarization and relaxation via nitric oxide release in the circular muscle of the guinea-pig colon. Regulatory peptides 31 7531357
2011 Decreased methylation of the NK3 receptor coding gene (TACR3) after cocaine-induced place preference in marmoset monkeys. Addiction biology 30 22070124
1997 Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord. The Journal of comparative neurology 30 9136801
1996 Study of SR 142801, a new potent non-peptide NK3 receptor antagonist on cardiovascular responses in conscious guinea-pig. British journal of pharmacology 30 8818331
2008 New quinoline NK3 receptor antagonists with CNS activity. Bioorganic & medicinal chemistry letters 29 19117759
2005 Receptors and counterreceptors involved in NK-B cell interactions. Journal of immunology (Baltimore, Md. : 1950) 29 15778370
2000 Neurokinin B- and specific tachykinin NK(3) receptor agonists-induced airway hyperresponsiveness in the guinea-pig. British journal of pharmacology 29 10780997
2000 Tachykinin NK1 and NK3 receptors in the prefrontal cortex of the human brain. Clinical and experimental pharmacology & physiology 29 11071316
2010 Therapeutic utility of NK3 receptor antagonists for the treatment of schizophrenia. Current pharmaceutical design 28 20109143
2006 Neuroprotective role of neurokinin B (NKB) on beta-amyloid (25-35) induced toxicity in aging rat brain synaptosomes: involvement in oxidative stress and excitotoxicity. Biogerontology 28 16518716
2002 Neurokinin NK1- and NK3-immunoreactive neurons in serotonergic cell groups in the rat brain. Neuroscience letters 28 11950514
1997 Immunocytochemical detection of the neurokinin B receptor (NK3) on melanin-concentrating hormone (MCH) neurons in rat brain. Journal of chemical neuroanatomy 28 9141650
1997 Cardiovascular and behavioural effects of intracerebroventricularly administered tachykinin NK3 receptor antagonists in the conscious rat. British journal of pharmacology 28 9375960
1997 Tachykinin NK-1 and NK-3 selective agonists induce analgesia in the formalin test for tonic pain following intra-VTA or intra-accumbens microinfusions. Behavioural brain research 28 9475623
2006 The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys. European journal of pharmacology 27 16603151
2005 Agonist and hypertonic saline-induced trafficking of the NK3-receptors on vasopressin neurons within the paraventricular nucleus of the hypothalamus. American journal of physiology. Regulatory, integrative and comparative physiology 27 16357093
2006 Distribution and pharmacological characterization of primate NK-1 and NK-3 tachykinin receptors in the central nervous system of the rhesus monkey. British journal of pharmacology 26 16331282
2005 Randomized, double-blind study of SR142801 (Osanetant). A novel neurokinin-3 (NK3) receptor antagonist in panic disorder with pre- and posttreatment cholecystokinin tetrapeptide (CCK-4) challenges. Pharmacopsychiatry 26 15706463
2003 Tachykinin NK3 and NK1 receptor activation elicits secretion from porcine airway submucosal glands. British journal of pharmacology 26 12522097
1996 Evidence for modulation of dopamine-neuronal function by tachykinin NK3 receptor stimulation in gerbil mesencephalic cell cultures. The European journal of neuroscience 26 9081631
1991 Characterization of NK-3 binding sites in rat and guinea pig cortical membranes by the selective ligand [3H]Senktide. Neuropeptides 26 1712430
1991 The presence of NK3 tachykinin receptors on rat uterus. European journal of pharmacology 25 1724757
2009 The human neurokinin B gene, TAC3, and its promoter are regulated by Neuron Restrictive Silencing Factor (NRSF) transcription factor family. Neuropeptides 24 19539370
1999 Postnatal development of NK1, NK2, and NK3 neurokinin receptors expression in the rat retina. Brain research. Developmental brain research 24 10536233
1995 Autoradiographic localization of NK1 and NK3 tachykinin receptors in rat kidney. Peptides 24 7479302
1995 Functional interaction between losartan and central tachykinin NK3 receptors in the conscious rat. British journal of pharmacology 24 7541280
1995 Modulation of neurotransmitter receptors following unilateral L1-S2 deafferentation: NK1, NK3, NMDA, and 5HT1a receptor binding autoradiography. The Journal of comparative neurology 24 8576419
2002 Biochemical and pharmacological activities of SSR 146977, a new potent nonpeptide tachykinin NK3 receptor antagonist. Canadian journal of physiology and pharmacology 23 12056557
1997 Localization of Fos-like immunoreactivity induced by the NK3 tachykinin receptor agonist, senktide, in the guinea-pig brain. British journal of pharmacology 23 9375969
1994 Identification of methionine134 and alanine146 in the second transmembrane segment of the human tachykinin NK3 receptor as reduces involved in species-selective binding to SR 48968. Biochemical and biophysical research communications 23 8117303
1994 The non-peptide tachykinin NK2 receptor antagonist SR 48968 interacts with human, but not rat, cloned tachykinin NK3 receptors. Biochemical and biophysical research communications 23 8117304
2010 Peristalsis and fecal pellet propulsion do not require nicotinic, purinergic, 5-HT3, or NK3 receptors in isolated guinea pig distal colon. American journal of physiology. Gastrointestinal and liver physiology 22 20360134
2008 NK(3) receptor agonism promotes episodic-like memory in mice. Neurobiology of learning and memory 22 18556225
1998 Canine intrinsic cardiac neurons involved in cardiac regulation possess NK1, NK2, and NK3 receptors. The American journal of physiology 22 9791091
1997 A tachykinin NK3 receptor antagonist, SR 142801 (osanetant), prevents substance P-induced bronchial hyperreactivity in guinea-pigs. Pulmonary pharmacology & therapeutics 22 9778489
1995 Functional characterization of the human neurokinin receptors NK1, NK2, and NK3 based on a cellular assay system. Journal of receptor and signal transduction research 22 8903968
2001 Cholinergic neurons expressing neuromedin K receptor (NK3) in the basal forebrain of the rat: a double immunofluorescence study. Neuroscience 21 11246156
2000 Independent endocytosis of the NK(1) and NK(3) tachykinin receptors in neurons of the rat myenteric plexus. Neuroscience 21 10996469
2019 Pre-activation of TLR3 enhances the therapeutic effect of BMMSCs through regulation the intestinal HIF-2α signaling pathway and balance of NKB cells in experimental alcoholic liver injury. International immunopharmacology 20 30870678
2018 NKB signaling in the posterodorsal medial amygdala stimulates gonadotropin release in a kisspeptin-independent manner in female mice. eLife 20 30565563
2008 Neurokinin B/NK3 receptors exert feedback inhibition on L-DOPA actions in the 6-OHDA lesion rat model of Parkinson's disease. Neuropharmacology 20 18423776
2000 SR142801 behaves as a tachykinin NK-3 receptor agonist on a spinal nociceptive reflex in the rat. Life sciences 20 10658924
1996 Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular nucleus. Brain research 20 9017229
1995 Effect of SR 142801 on nitric oxide-dependent and independent responses to tachykinin NK3 receptor agonists in isolated guinea-pig colon. Naunyn-Schmiedeberg's archives of pharmacology 20 8751080
2011 Molecular modeling of neurokinin B and tachykinin NK₃ receptor complex. Journal of chemical information and modeling 19 21913652
2010 Novel NK(3) receptor antagonists for the treatment of schizophrenia and other CNS indications. Current opinion in drug discovery & development 19 20597024
2006 N',2-diphenylquinoline-4-carbohydrazide based NK3 receptor antagonists. Bioorganic & medicinal chemistry letters 19 16950620
1997 Characterization of NK3 receptors in rabbit isolated iris sphincter muscle. British journal of pharmacology 19 9117105
1992 Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus. Brain research 19 1281741
2013 Differentially regulated expression of neurokinin B (NKB)/NK3 receptor system in uterine leiomyomata. Human reproduction (Oxford, England) 18 23656837
1995 Nitric oxide is a mediator of tachykinin NK3 receptor-induced relaxation in rat mesenteric artery. British journal of pharmacology 18 8680725
1994 GR138676, a novel peptidic tachykinin antagonist which is potent at NK3 receptors. Neuropeptides 18 7534879
2011 Discovery of 3-aryl-5-acylpiperazinyl-pyrazoles as antagonists to the NK3 receptor. Bioorganic & medicinal chemistry letters 17 21376585
2011 The NK3 receptor agonist senktide ameliorates scopolamine-induced deficits in memory for object, place and temporal order. Neurobiology of learning and memory 17 22209911
2004 Calcitonin gene-related peptide facilitates serotonin release from guinea-pig colonic mucosa via myenteric neurons and tachykinin NK2/NK3 receptors. British journal of pharmacology 17 14718265
1994 Non-peptide angiotensin receptor antagonists bind to tachykinin NK3 receptors of rat and guinea pig brain. European journal of pharmacology 17 7517891