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Katharina Domschke - One of the best experts on this subject based on the ideXlab platform.

  • Neuropeptide S Receptor Gene Variation Differentially ModulateS Fronto-Limbic Effective Connectivity in Childhood and AdoleScence
    Cerebral Cortex, 2015
    Co-Authors: Katharina Domschke, Atae Akhrif, Marcel Romanos, Christina Bajer, Margrit Mainusch, Juliane Winkelmann, Claus Zimmer, Susanne Neufang
    Abstract:

    The Neuropeptide S (NPS) SyStem contributeS to the pathogeneSiS of anxiety. The more active T allele of the functional rS324981 variant in the Neuropeptide S receptor gene (NPSR1) iS aSSociated with panic diSorder (PD) and diStorted cortico-limbic activity during emotion proceSSing in healthy adultS and PD patientS. ThiS Study inveStigated the influence of NPSR1 genotype on fronto-limbic effective connectivity within the developing brain. Sixty healthy SubjectS (8-21 yearS) were examined uSing an emotional go-nogo taSk and fMRI. Fronto-limbic connectivity waS determined uSing Dynamic CauSal Modeling. In A allele carrierS, connectivity between the right middle frontal gyruS (MFG) and the right amygdala waS higher in older (≥14 yearS) than that in younger (

  • Neuropeptide S receptor gene variation modulateS anterior cingulate cortex glx levelS during cck 4 induced panic
    European Neuropsychopharmacology, 2015
    Co-Authors: Tillmann Ruland, Katharina Domschke, Valerie Schutte, Maxim Zavorotnyy, Harald Kugel, Swantje Notzon, Nadja Vennewald, Patricia Ohrmann, Volker Arolt
    Abstract:

    AbStract An excitatory-inhibitory neurotranSmitter dySbalance haS been SuggeSted in pathogeneSiS of panic diSorder. The Neuropeptide S (NPS) SyStem haS been implicated in modulating GABA and glutamate neurotranSmiSSion in animal modelS and to genetically drive altered fear circuit function and an increaSed riSk of panic diSorder in humanS. Probing a multi-level imaging genetic riSk model of panic, in the preSent magnetic reSonance SpectroScopy (MRS) Study brain glutamate+glutamine (Glx) levelS in the bilateral anterior cingulate cortex (ACC) during a pharmacological cholecyStokinin tetrapeptide (CCK-4) panic challenge were aSSeSSed depending on the functional Neuropeptide S receptor gene ( NPSR1 ) rS324981 A/T variant in a final Sample of 35 healthy male SubjectS. The Subjective panic reSponSe (Panic Symptom Scale; PSS) aS well aS cortiSol and ACTH levelS were aScertained throughout the experiment. CCK-4 injection waS followed by a Strong panic reSponSe. A Significant time×genotype interaction waS detected ( p =.008), with Significantly lower ACC Glx/Cr levelS in T allele carrierS aS compared to AA homozygoteS 5 min after injection ( p =.003). CCK-4 induced Significant HPA axiS Stimulation, but no effect of genotype waS diScerned. The preSent pilot data SuggeStS NPSR1 gene variation to modulate Glx levelS in the ACC during acute StateS of StreSS and anxiety, with blunted, i.e. poSSibly maladaptive ACC glutamatergic reactivity in T riSk allele carrierS. Our reSultS underline the notion of a genetically driven rapid and dynamic reSponSe mechaniSm in the neural regulation of human anxiety and further Strengthen the emerging role of the NPS SyStem in anxiety.

  • Interaction of the Neuropeptide S receptor gene ASn107Ile variant and environment: contribution to affective and anxiety diSorderS, and Suicidal behaviour
    The International Journal of Neuropsychopharmacology, 2013
    Co-Authors: Kariina Laas, Katharina Domschke, Andreas Reif, Kirsti Akkermann, Evelyn Kiive, Klaus-peter Lesch, Toomas Veidebaum, Jaanus Harro
    Abstract:

    Neuropeptide S iS involved in anxiety and arouSal modulation, and the functional polymorphiSm ASn107Ile (rS324981, A > T) of the Neuropeptide S receptor gene ( NPSR1 ) iS aSSociated with panic diSorder and anxiety/fear-related traitS. NPSR1 alSo interactS with the environment in Shaping perSonality and impulSivity. We therefore examined whether the NPSR1 A/T polymorphiSm iS aSSociated with affective and anxiety diSorderS in a population-repreSentative Sample. Lifetime pSychiatric diSorderS were aSSeSSed by MINI interview ( n = 501) in the older cohort of the longitudinal EStonian Children PerSonality, Behaviour and Health Study (ECPBHS). Anxiety (STAI), Self-eSteem (RSES), depreSSion (MADRS), Suicide attemptS and environmental factorS were Self-reported in both the younger (original n = 583) and the older cohort (original n = 593). MoSt of the NPSR1 effectS were Sex-Specific and depended on environmental factorS. FemaleS with the functionally leaSt active NPSR1 AA genotype and expoSed to environmental adverSity had affective/anxiety diSorderS more frequently; they alSo exhibited higher anxiety and depreSSiveneSS, and lower Self-eSteem. Female AA homozygoteS alSo reported Suicidal behaviour more frequently, and thiS waS further accentuated by adverSe family environment. In the general population, the NPSR1 A/T polymorphiSm together with environmental factorS iS aSSociated with anxiouS, depreSSive and activity-related traitS, increaSed prevalence of affective/anxiety diSorderS and a higher likelihood of Suicidal behaviour.

  • Neuropeptide S receptor gene fear Specific modulationS of prefrontal activation
    NeuroImage, 2013
    Co-Authors: Katharina Domschke, Martin J. Herrmann, Andreas Reif, Sara V Tupak, Paul Pauli, Thomas Dresler, Clara Jochum
    Abstract:

    Since central adminiStration of Neuropeptide S (NPS) haS been Shown to exert anxiolytic effectS on rodent behavior in a number of StudieS, genetic variantS of itS cognate G-protein coupled receptor (NPSR1) became the focuS of Several recent human StudieS on anxiety and anxiety diSorderS. The T allele of rS324981, which goeS along with enhanced receptor function, waS aSSociated with panic diSorder, increaSed anxiety SenSitivity in healthy SubjectS, attenuated prefrontal brain activation and elevated amygdala reSponSeS to fear-relevant Stimuli. To inveStigate whether prefrontal attenuationS in rS324981 T allele carrierS are Specific to fear-relevant StimuluS content and cannot be attributed to a generally higher interference of emotional Stimuli, 92 SubjectS performed a combined cognitive and emotional Stroop taSk while oxygenation changeS in the prefrontal cortex were recorded uSing functional near-infrared SpectroScopy. ReSultS Showed a Specific NPSR1 gene activation modulation in reSponSe to fear-relevant word Stimuli. Only A-homozygoteS diSplayed an emotional Stroop effect in termS of increaSed activation to fear-relevant Stimuli in medial and dorSolateral prefrontal cortex. Specifically, activation in the fear-relevant condition waS higher in A-homozygoteS aS compared to T allele carrierS while no group differenceS were found during neutral, congruent or highly interfering incongruent color word preSentation. The current reSultS are in line with earlier imaging genetic StudieS and SuggeSt a potential protective function of the NPSR1 rS324981 A/A genotype againSt pathologically enhanced anxiety that might be explained by Stronger reflective prefrontal regulation over the Subcortical fear reSponSe.

  • Neuropeptide S receptor (NPSR1) gene variation modulateS reSponSe inhibition and error monitoring
    NeuroImage, 2013
    Co-Authors: Christian Beste, Carsten Konrad, Christina Uhlmann, Volker Arolt, Peter Zwanzger, Katharina Domschke
    Abstract:

    AbStract The Neuropeptide S (NPS) SyStem haS been SuggeSted to contribute to the pathogeneSiS of anxiety. In order to further characterize the cognitive-neurophySiological relevance of Neuropeptide S in the etiology of anxiety, the influence of a functional Neuropeptide S receptor gene (NPSR1) variant on reSponSe inhibition and error monitoring waS inveStigated under conSideration of the dimenSional phenotype of anxiety SenSitivity (AS). In a Sample of N = 97 healthy probandS, event-related potential (ERP) meaSurement uSing a modified Flanker taSk waS applied allowing for a diStinct neurophySiological examination of proceSSeS related to reSponSe inhibition (Nogo-N2, Nogo-P3) and error monitoring (Ne/ERN). All SubjectS were genotyped for the functional NPSR1 A/T (ASn107Ile) variant (rS324981) and characterized for anxiety SenSitivity uSing the Anxiety SenSitivity Index (ASI). CarrierS of the NPSR1 T allele diSplayed intenSified reSponSe inhibition (Nogo-P3) and error monitoring (Ne/ERN), which waS in both caSeS paralleled by the behavioral data. Furthermore, anxiety SenSitivity waS found to be higher in NPSR1 T allele carrierS and to correlate with Nogo-P3 and Ne/ERN. A mediation analySiS revealed the ERN to mediate the effect between NPSR1 genotype and anxiety SenSitivity. In Summary, the more active NPSR1 T allele may confer enhanced reSponSe inhibition and increaSed error monitoring and might drive particularly error monitoring aS a neurophySiological endophenotype of anxiety aS reflected by increaSed anxiety SenSitivity. TheSe findingS further corroborate a major role of the Neuropeptide S SyStem in the pathogeneSiS of anxiety and SuggeSt a potentially beneficial uSe of therapeutic agentS targeting the NPS SyStem in anxiety diSorderS.

Rainer K. Reinscheid - One of the best experts on this subject based on the ideXlab platform.

  • Neuropeptide S receptor (verSion 2019.4) in the IUPHAR/BPS Guide to Pharmacology DatabaSe
    IUPHAR BPS Guide to Pharmacology CITE, 2019
    Co-Authors: Girolamo Calo, Olivier Civelli, Rainer K. Reinscheid, Chiara Ruzza
    Abstract:

    The Neuropeptide S receptor (NPS, proviSional nomenclature [18]) reSpondS to the 20 amino-acid peptide Neuropeptide S derived from a precurSor (NPS, P0C0P6).

  • Pharmacological profile of the Neuropeptide S receptor: Dynamic maSS rediStribution StudieS.
    Pharmacology Research & Perspectives, 2018
    Co-Authors: Chiara Ruzza, Remo Guerrini, Rainer K. Reinscheid, Erika Marzola, Federica Ferrari, Delia Preti, Girolamo Calo
    Abstract:

    Neuropeptide S (NPS) iS the endogenouS ligand of the Neuropeptide S receptor (NPSR). NPS modulateS Several biological functionS including anxiety, wakefulneSS, pain, and drug abuSe. The aim of thiS Study waS the inveStigation of the pharmacological profile of NPSR uSing the dynamic maSS rediStribution (DMR) aSSay. DMR iS a label-free aSSay that offerS a holiStic view of cellular reSponSeS after receptor activation. HEK293 cellS Stably tranSfected with the murine NPSR (HEK293mNPSR) have been uSed. To inveStigate the nature of the NPS-evoked DMR Signaling, FR900359 (Gq inhibitor), pertuSSiS toxin (Gi inhibitor), and rolipram (phoSphodieSteraSe inhibitor) were uSed. To determine the pharmacology of NPSR, Several Selective ligandS (agoniStS, partial agoniStS, antagoniStS) have been teSted. NPS, through Selective NPSR activation, evoked a robuSt DMR Signal with potency in the nanomolar range. ThiS Signal waS predominantly, but not completely, blocked by FR900359, SuggeSting the involvement of the Gq-dependent Signaling caScade. NPSR ligandS (agoniStS and antagoniStS) diSplayed potency valueS in DMR experimentS Similar, but not identical, to thoSe reported in the literature. Furthermore, partial agoniStS produced a higher efficacy in DMR than in calcium experimentS. DMR can be SucceSSfully uSed to Study the pharmacology and Signaling propertieS of novel NPSR ligandS. ThiS innovative approach will likely increaSe the tranSlational value of in vitro pharmacological StudieS.

  • Neuropeptide S precurSor knockout mice diSplay memory and arouSal deficitS
    European Journal of Neuroscience, 2017
    Co-Authors: Xiaobin Liu, Kay Jungling, Hanschristian Pape, Celia Garau, Stefan Schulz, Rainer K. Reinscheid
    Abstract:

    Activation of Neuropeptide S (NPS) Signaling haS been found to produce arouSal, wakefulneSS, anxiolytic-like behaviorS, and enhanced memory formation. In order to further Study phySiological functionS of the NPS SyStem, we generated NPS precurSor knockout mice by homologouS recombination in embryonic Stem cellS. NPS−/− mice were viable, fertile, and anatomically normal, when compared to their wild-type and heterozygouS littermateS. The total number of NPS neuronS—although no longer SyntheSizing the peptide – waS not affected by the knockout, aS analyzed in NPS−/−/NPSEGFP double tranSgenic mice. AnalySiS of behavioral phenotypeS revealed Significant deficitS in exploratory activity in NPS−/− mice. NPS precurSor knockout mice diSplayed attenuated arouSal in the hole board teSt, viSible aS reduced total noSe pokeS and number of holeS inSpected, that waS not confounded by increaSed repetitive or Stereotypic behavior. Importantly, long-term memory waS Significantly impaired in NPS−/− mice in the inhibitory avoidance paradigm. NPS precurSor knockout mice diSplayed mildly increaSed anxiety-like behaviorS in three different teStS meaSuring reSponSeS to StreSS and novelty. IntereStingly, heterozygouS littermateS often preSented behavioral deficitS Similar to NPS−/− mice or diSplayed intermediate phenotype. TheSe obServationS may SuggeSt limited ligand availability in critical neural circuitS. Overall, phenotypical changeS in NPS−/− mice are Similar to thoSe obServed in NPS receptor knockout mice and Support earlier findingS that SuggeSt major functionS of the NPS SyStem in arouSal, regulation of anxiety and StreSS, and memory formation.

  • Identification of Neuropeptide S antagoniStS: Structure-activity relationShip StudieS, X-ray cryStallography, and in vivo evaluation.
    ACS Chemical Neuroscience, 2014
    Co-Authors: Carla Hassler, Rainer K. Reinscheid, Yanan Zhang, Brian P. Gilmour, Tyler N. Graf, Timothy R. Fennell, Rodney W. Snyder, Jeffrey R. Deschamps, Celia Garau, Scott P. Runyon
    Abstract:

    Modulation of the Neuropeptide S (NPS) SyStem haS been linked to a variety of CNS diSorderS Such aS panic diSorder, anxiety, Sleeping diSorderS, aSthma, obeSity, PTSD, and SubStance abuSe. In thiS Study, a SerieS of diphenyltetrahydro-1H-oxazolo[3,4-α]pyrazin-3(5H)-oneS were SyntheSized and evaluated for antagoniSt activity at the Neuropeptide S receptor. The abSolute configuration waS determined by chiral reSolution of the key Synthetic intermediate, followed by analySiS of one of the individual enantiomerS by X-ray cryStallography. The R iSomer waS then converted to a biologically active compound (34) that had a Ke of 36 nM. The moSt potent compound diSplayed enhanced aqueouS Solubility compared with the prototypical antagoniSt SHA-68 and demonStrated favorable pharmacokinetic propertieS for behavioral aSSeSSment. In vivo analySiS in mice indicated a Significant blockade of NPS induced locomotor activity at an ip doSe of 50 mg/kg. ThiS SuggeStS that analogS having improved drug-like propertieS will faci...

  • Anatomical characterization of the Neuropeptide S SyStem in the mouSe brain by in Situ hybridization and immunohiStochemiStry.
    The Journal of Comparative Neurology, 2011
    Co-Authors: Stewart D. Clark, Dee M. Duangdao, Stefan Schulz, Li Zhang, Xiaobin Liu, Rainer K. Reinscheid
    Abstract:

    Neuropeptide S (NPS) iS the endogenouS ligand for GPR154, now referred to aS Neuropeptide S receptor (NPSR). PhySiologically, NPS haS been characterized aS a modulator of arouSal and haS been Shown to produce anxiolytic-like effectS in rodentS. Neuroanatomical analySiS in the rat revealed that the NPS precurSor mRNA iS Strongly expreSSed in the brainStem in only three diStinct regionS: the locuS coeruleuS area, the principal SenSory trigeminal nucleuS, and the lateral parabrachial nucleuS. NPSR mRNA expreSSion in the rat iS widely diStributed, with the StrongeSt expreSSion in the olfactory nuclei, amygdala, Subiculum, and Some cortical StructureS, aS well aS variouS thalamic and hypothalamic regionS. Here we report a comprehenSive map of NPS precurSor and receptor mRNA expreSSion in the mouSe brain. NPS precurSor mRNA iS only expreSSed in two regionS in the mouSe brainStem: the Kolliker-FuSe nucleuS and the pericoerulear area. Strong NPSR mRNA expreSSion waS found in the dorSal endopiriform nucleuS, the intra-midline thalamic and hypothalamic regionS, the baSolateral amgydala, the Subiculum, and variouS cortical regionS. In order to elucidate projectionS from NPS-producing nuclei in the brainStem to NPSR-expreSSing StructureS throughout the brain, we performed immunohiStochemical analySiS in the mouSe brain by uSing two polyclonal anti-NPS antiSera. The diStribution of NPS-immunopoSitive fiberS overlapS well with NPSR mRNA expreSSion in thalamic and hypothalamic regionS. MiSmatcheS between NPSR expreSSion and NPS-immunoreactive fiber Staining were obServed in hippocampal, olfactory, and cortical regionS. TheSe data demonStrate that the diStribution pattern of the central NPS SyStem iS only partially conServed between mice and ratS.

Remo Guerrini - One of the best experts on this subject based on the ideXlab platform.

  • Pharmacological profile of the Neuropeptide S receptor: Dynamic maSS rediStribution StudieS.
    Pharmacology Research & Perspectives, 2018
    Co-Authors: Chiara Ruzza, Remo Guerrini, Rainer K. Reinscheid, Erika Marzola, Federica Ferrari, Delia Preti, Girolamo Calo
    Abstract:

    Neuropeptide S (NPS) iS the endogenouS ligand of the Neuropeptide S receptor (NPSR). NPS modulateS Several biological functionS including anxiety, wakefulneSS, pain, and drug abuSe. The aim of thiS Study waS the inveStigation of the pharmacological profile of NPSR uSing the dynamic maSS rediStribution (DMR) aSSay. DMR iS a label-free aSSay that offerS a holiStic view of cellular reSponSeS after receptor activation. HEK293 cellS Stably tranSfected with the murine NPSR (HEK293mNPSR) have been uSed. To inveStigate the nature of the NPS-evoked DMR Signaling, FR900359 (Gq inhibitor), pertuSSiS toxin (Gi inhibitor), and rolipram (phoSphodieSteraSe inhibitor) were uSed. To determine the pharmacology of NPSR, Several Selective ligandS (agoniStS, partial agoniStS, antagoniStS) have been teSted. NPS, through Selective NPSR activation, evoked a robuSt DMR Signal with potency in the nanomolar range. ThiS Signal waS predominantly, but not completely, blocked by FR900359, SuggeSting the involvement of the Gq-dependent Signaling caScade. NPSR ligandS (agoniStS and antagoniStS) diSplayed potency valueS in DMR experimentS Similar, but not identical, to thoSe reported in the literature. Furthermore, partial agoniStS produced a higher efficacy in DMR than in calcium experimentS. DMR can be SucceSSfully uSed to Study the pharmacology and Signaling propertieS of novel NPSR ligandS. ThiS innovative approach will likely increaSe the tranSlational value of in vitro pharmacological StudieS.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S
    Journal of Anesthesia, 2018
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine (DSP-4). MethodS A total 66 male Sprague–Dawley ratS weighing 350–450 g were uSed. AnalgeSic effectS of NPS were evaluated uSing hot-plate and tail-flick teSt with or without DSP-4. The animal allocated into 3 groupS; hot-plate with NPS alone intracerebroventricular (icv) (0.0, 1.0, 3.3, and 10.0 nmol), tail-flick NPS alone icv (0.0 and 10.0 nmol), and hot-plate with NPS and DSP-4 (0 or 50 mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, ponS, hypothalamuS, were meaSured. ReSultS NPS 10 nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40 min after adminiStration. DSP-4 50 mg/kg decreaSed noradrenaline content in the all 3 regionS. The NA depletion inhibited NPS analgeSic effect in the hot plate teSt but not tail flick teSt. There waS a Significant correlation between hot plate latency (percentage of maximum poSSible effect: %MPE) with NPS 10 nmol and NA content in the cerebral cortex ( p  = 0.017, r ^2 = 0.346) which noradrenergic innervation ariSen mainly from the LC. No other regionS had the correlation. ConcluSionS NPS analgeSia interactS with LC noradrenergic neuronal activity.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S.
    Journal of Anesthesia, 2017
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4).

  • Neuropeptide S receptor ligandS: a patent review (2005-2016).
    Expert Opinion on Therapeutic Patents, 2016
    Co-Authors: Chiara Ruzza, Claudio Trapella, Girolamo Calo, Delia Preti, Salvatore Di Maro, Salvatore Pacifico, Severo Salvadori, Remo Guerrini
    Abstract:

    ABSTRACTIntroduction: Neuropeptide S (NPS) iS a 20-reSidue peptide and endogenouS ligand of the NPS receptor (NPSR). ThiS receptor waS a formerly orphan GPCR whoSe activation increaSeS calcium and cyclic adenoSine monophoSphate levelS. The NPS/NPSR SyStem iS expreSSed in Several brain regionS where it controlS important biological functionS including locomotor activity, arouSal and Sleep, anxiety, food intake, memory, pain, and drug addiction.AreaS covered: ThiS review furniSheS an updated overview of the patent literature covering NPSR ligandS Since 2005, when the firSt example of an NPSR antagoniSt waS diScloSed.Expert opinion: Several potent NPSR antagoniStS are available aS valuable pharmacological toolS deSpite Showing Suboptimal pharmacokinetic propertieS in vivo. The optimization of theSe ligandS iS needed to Speed up their potential clinical advancement aS pharmaceuticalS to treat drug addiction. In order to Support the deSign of novel NPSR antagoniStS, we performed a ligand-baSed conformational a...

  • Neuropeptide S reduceS mouSe aggreSSiveneSS in the reSident/intruder teSt through Selective activation of the Neuropeptide S receptor
    Neuropharmacology, 2015
    Co-Authors: Chiara Ruzza, Laila Asth, Remo Guerrini, Claudio Trapella, Elaine C Gavioli
    Abstract:

    AbStract Neuropeptide S (NPS) regulateS variouS biological functionS by Selectively activating the NPS receptor (NPSR). In particular NPS evokeS robuSt anxiolytic-like effectS in rodentS together with a Stimulant and arouSal promoting action. The aim of the Study waS to inveStigate the effectS of NPS on the aggreSSiveneSS of mice Subjected to the reSident/intruder teSt. Moreover the putative role played by the endogenouS NPS/NPSR SyStem in regulating mice aggreSSiveneSS waS inveStigating uSing mice lacking the NPSR receptor (NPSR(−/−)) and the NPSR Selective antagoniStS [tBu-D-Gly5]NPS and SHA 68. NPS (0.01–1 nmol, icv) reduced, in a doSe dependent manner, both the time that reSident mice Spent attacking the intruder mice and their number of attackS, producing pharmacological effectS Similar to thoSe elicited by the Standard anti-aggreSSive drug valproate (300 mg/kg, ip). ThiS NPS effect waS evident in NPSR wild type (NPSR(+/+)) mice but completely diSappeared in NPSR(−/−) mice. Moreover, NPSR(−/−) mice diSplayed a Significantly higher time Spent attacking than NPSR(+/+) mice. [tBu-D-Gly5]NPS (10 nmol, icv) did not change the behavior of mice in the reSident/intruder teSt but completely counteracted NPS effectS. SHA 68 (50 mg/kg, ip) waS inactive per Se and againSt NPS. In concluSion, thiS Study demonStrated that NPS produceS anti-aggreSSive effectS in mice through the Selective activation of NPSR and that the endogenouS NPS/NPSR SyStem can exert a role in the control of aggreSSiveneSS levelS under the preSent experimental conditionS.

Girolamo Calo - One of the best experts on this subject based on the ideXlab platform.

  • Neuropeptide S receptor (verSion 2019.4) in the IUPHAR/BPS Guide to Pharmacology DatabaSe
    IUPHAR BPS Guide to Pharmacology CITE, 2019
    Co-Authors: Girolamo Calo, Olivier Civelli, Rainer K. Reinscheid, Chiara Ruzza
    Abstract:

    The Neuropeptide S receptor (NPS, proviSional nomenclature [18]) reSpondS to the 20 amino-acid peptide Neuropeptide S derived from a precurSor (NPS, P0C0P6).

  • Pharmacological profile of the Neuropeptide S receptor: Dynamic maSS rediStribution StudieS.
    Pharmacology Research & Perspectives, 2018
    Co-Authors: Chiara Ruzza, Remo Guerrini, Rainer K. Reinscheid, Erika Marzola, Federica Ferrari, Delia Preti, Girolamo Calo
    Abstract:

    Neuropeptide S (NPS) iS the endogenouS ligand of the Neuropeptide S receptor (NPSR). NPS modulateS Several biological functionS including anxiety, wakefulneSS, pain, and drug abuSe. The aim of thiS Study waS the inveStigation of the pharmacological profile of NPSR uSing the dynamic maSS rediStribution (DMR) aSSay. DMR iS a label-free aSSay that offerS a holiStic view of cellular reSponSeS after receptor activation. HEK293 cellS Stably tranSfected with the murine NPSR (HEK293mNPSR) have been uSed. To inveStigate the nature of the NPS-evoked DMR Signaling, FR900359 (Gq inhibitor), pertuSSiS toxin (Gi inhibitor), and rolipram (phoSphodieSteraSe inhibitor) were uSed. To determine the pharmacology of NPSR, Several Selective ligandS (agoniStS, partial agoniStS, antagoniStS) have been teSted. NPS, through Selective NPSR activation, evoked a robuSt DMR Signal with potency in the nanomolar range. ThiS Signal waS predominantly, but not completely, blocked by FR900359, SuggeSting the involvement of the Gq-dependent Signaling caScade. NPSR ligandS (agoniStS and antagoniStS) diSplayed potency valueS in DMR experimentS Similar, but not identical, to thoSe reported in the literature. Furthermore, partial agoniStS produced a higher efficacy in DMR than in calcium experimentS. DMR can be SucceSSfully uSed to Study the pharmacology and Signaling propertieS of novel NPSR ligandS. ThiS innovative approach will likely increaSe the tranSlational value of in vitro pharmacological StudieS.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S
    Journal of Anesthesia, 2018
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine (DSP-4). MethodS A total 66 male Sprague–Dawley ratS weighing 350–450 g were uSed. AnalgeSic effectS of NPS were evaluated uSing hot-plate and tail-flick teSt with or without DSP-4. The animal allocated into 3 groupS; hot-plate with NPS alone intracerebroventricular (icv) (0.0, 1.0, 3.3, and 10.0 nmol), tail-flick NPS alone icv (0.0 and 10.0 nmol), and hot-plate with NPS and DSP-4 (0 or 50 mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, ponS, hypothalamuS, were meaSured. ReSultS NPS 10 nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40 min after adminiStration. DSP-4 50 mg/kg decreaSed noradrenaline content in the all 3 regionS. The NA depletion inhibited NPS analgeSic effect in the hot plate teSt but not tail flick teSt. There waS a Significant correlation between hot plate latency (percentage of maximum poSSible effect: %MPE) with NPS 10 nmol and NA content in the cerebral cortex ( p  = 0.017, r ^2 = 0.346) which noradrenergic innervation ariSen mainly from the LC. No other regionS had the correlation. ConcluSionS NPS analgeSia interactS with LC noradrenergic neuronal activity.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S.
    Journal of Anesthesia, 2017
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4).

  • Neuropeptide S receptor ligandS: a patent review (2005-2016).
    Expert Opinion on Therapeutic Patents, 2016
    Co-Authors: Chiara Ruzza, Claudio Trapella, Girolamo Calo, Delia Preti, Salvatore Di Maro, Salvatore Pacifico, Severo Salvadori, Remo Guerrini
    Abstract:

    ABSTRACTIntroduction: Neuropeptide S (NPS) iS a 20-reSidue peptide and endogenouS ligand of the NPS receptor (NPSR). ThiS receptor waS a formerly orphan GPCR whoSe activation increaSeS calcium and cyclic adenoSine monophoSphate levelS. The NPS/NPSR SyStem iS expreSSed in Several brain regionS where it controlS important biological functionS including locomotor activity, arouSal and Sleep, anxiety, food intake, memory, pain, and drug addiction.AreaS covered: ThiS review furniSheS an updated overview of the patent literature covering NPSR ligandS Since 2005, when the firSt example of an NPSR antagoniSt waS diScloSed.Expert opinion: Several potent NPSR antagoniStS are available aS valuable pharmacological toolS deSpite Showing Suboptimal pharmacokinetic propertieS in vivo. The optimization of theSe ligandS iS needed to Speed up their potential clinical advancement aS pharmaceuticalS to treat drug addiction. In order to Support the deSign of novel NPSR antagoniStS, we performed a ligand-baSed conformational a...

Kazuyoshi Hirota - One of the best experts on this subject based on the ideXlab platform.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S
    Journal of Anesthesia, 2018
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N -(2-chloroethyl)- N -ethyl-2-bromobenzylamine (DSP-4). MethodS A total 66 male Sprague–Dawley ratS weighing 350–450 g were uSed. AnalgeSic effectS of NPS were evaluated uSing hot-plate and tail-flick teSt with or without DSP-4. The animal allocated into 3 groupS; hot-plate with NPS alone intracerebroventricular (icv) (0.0, 1.0, 3.3, and 10.0 nmol), tail-flick NPS alone icv (0.0 and 10.0 nmol), and hot-plate with NPS and DSP-4 (0 or 50 mg/kg ip). In hot-plate with NPS and DSP-4 group, noradrenaline content in the cerebral cortex, ponS, hypothalamuS, were meaSured. ReSultS NPS 10 nmol icv prolonged hot plate (%MPE) but not tail flick latency at 30 and 40 min after adminiStration. DSP-4 50 mg/kg decreaSed noradrenaline content in the all 3 regionS. The NA depletion inhibited NPS analgeSic effect in the hot plate teSt but not tail flick teSt. There waS a Significant correlation between hot plate latency (percentage of maximum poSSible effect: %MPE) with NPS 10 nmol and NA content in the cerebral cortex ( p  = 0.017, r ^2 = 0.346) which noradrenergic innervation ariSen mainly from the LC. No other regionS had the correlation. ConcluSionS NPS analgeSia interactS with LC noradrenergic neuronal activity.

  • Central noradrenergic activity affectS analgeSic effect of Neuropeptide S.
    Journal of Anesthesia, 2017
    Co-Authors: Kei Jinushi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Takashi Kudo, Kazuyoshi Hirota
    Abstract:

    Background Neuropeptide S (NPS) iS an endogenouS Neuropeptide controlling anxiolySiS, wakefulneSS, and analgeSia. NPS containing neuronS exiSt near to the locuS coeruleuS (LC) involved in the deScending anti-nociceptive SyStem. NPS interactS with central noradrenergic neuronS; thuS brain noradrenergic Signaling may be involved in NPS-induced analgeSia. We teSted NPS analgeSia in noradrenergic neuron-leSioned ratS uSing a Selective LC noradrenergic neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4).

  • endogenouS Neuropeptide S tone influenceS Sleep wake rhythm in ratS
    Neuroscience Letters, 2014
    Co-Authors: Masafumi Oishi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Hidetomo Niwa, Chihiro Yakoshi, Chihiro Ogasawara, Kazuyoshi Hirota
    Abstract:

    AbStract Neuropeptide S (NPS) iS an endogenouS peptide that exertS wakefulneSS promoting, analgeSic, and anxiolytic effectS when adminiStered exogenouSly. However, it remainS to be determined if endogenouS NPS tone iS involved in the control of the diurnal Sleep–wake cycle, or SpontanouS behavior. In thiS Study, we examined the effectS of the NPS receptor antagoniSt [D-CyS( t Bu) 5 ]NPS (2 and 20 nmol, icv) on phySiological Sleep and SpontaneouS locomotor behavior. The higher doSe of [D-CyS( t Bu) 5 ]NPS decreaSed the amount of time Spent in wakefulneSS [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p p t Bu) 5 ]NPS adminiStration. Collectively theSe data SuggeSt an involvement of the endogenouS NPS/NPS receptor SyStem in phySiological Sleep architecture.

  • EndogenouS Neuropeptide S tone influenceS Sleep-wake rhythm in ratS.
    Neuroscience Letters, 2014
    Co-Authors: Masafumi Oishi, Remo Guerrini, Girolamo Calo, Tetsuya Kushikata, Hidetomo Niwa, Chihiro Yakoshi, Chihiro Ogasawara, Kazuyoshi Hirota
    Abstract:

    Neuropeptide S (NPS) iS an endogenouS peptide that exertS wakefulneSS promoting, analgeSic, and anxiolytic effectS when adminiStered exogenouSly. However, it remainS to be determined if endogenouS NPS tone iS involved in the control of the diurnal Sleep-wake cycle, or SpontanouS behavior. In thiS Study, we examined the effectS of the NPS receptor antagoniSt [D-CyS((t)Bu)(5)]NPS (2 and 20 nmol, icv) on phySiological Sleep and SpontaneouS locomotor behavior. The higher doSe of [D-CyS((t)Bu)(5)]NPS decreaSed the amount of time Spent in wakefulneSS [control 782.5 ± 25.5 min, treatment 751.7 ± 28.1 min; p

  • The effectS of Neuropeptide S on general aneStheSia in ratS.
    Anesthesia & Analgesia, 2011
    Co-Authors: Tetsuya Kushikata, Girolamo Calo, Severo Salvadori, Hitoshi Yoshida, Mihoko Kudo, Kazuyoshi Hirota
    Abstract:

    BACKGROUND: Neuropeptide S (NPS) and itS receptor (NPSR) iS a novel Neuropeptide SyStem that regulateS arouSal and anxiety. A link between natural Sleep and general aneStheSia haS been SuggeSted. Therefore, we hypotheSized that the NPS neuronal SyStem may alSo modulate general aneStheSia. METHODS: The effectS of intracerebroventricular NPS and [D-CyS(tBu)5]NPS, a peptide NPSR antagoniSt, on ketamine and thiopental aneStheSia time were meaSured in ratS. AneStheSia time waS defined aS the interval between the loSS of righting reflex and itS recovery. RESULTS: Intracerebroventricular NPS 1 to 30 nmol Significantly reduced ketamine aneStheSia time, Showing a bell-Shaped doSe-reSponSe curve. [D-CyS(tBu)5]NPS 20 nmol antagonized NPS 1 nmol effectS and waS per Se able to increaSe ketamine aneStheSia time. Similar reSultS were obtained inveStigating thiopental aneStheSia time that waS Significantly reduced by NPS and prolonged by [D-CyS(tBu)5]NPS. CONCLUSION: NPS via Selective NPSR activation StimulateS the wakefulneSS-promoting pathway, thuS reducing aneStheSia duration. The endogenouS NPS/NPSR SyStem SeemS to tonically control theSe pathwayS.