Search results for "URB597"

showing 9 items of 9 documents

Chronic stress leads to epigenetic dysregulation in the neuropeptide-Y and cannabinoid CB1 receptor genes in the mouse cingulate cortex.

2017

Persistent stress triggers a variety of mechanisms, which may ultimately lead to the occurrence of anxiety- and depression-related disorders. Epigenetic modifications represent a mechanism by which chronic stress mediates long-term effects. Here, we analyzed brain tissue from mice exposed to chronic unpredictable stress (CUS), which induced impaired emotional and nociceptive behaviors. As endocannabinoid (eCB) and neuropeptide-Y (Npy) systems modulate emotional processes, we hypothesized that CUS may affect these systems through epigenetic mechanisms. We found reduced Npy expression and Npy type 1 receptor (Npy1r) signaling, and decreased expression of the cannabinoid type 1 receptor (CB1) …

0301 basic medicineCingulate cortexMalemedicine.medical_specialtyCannabinoid receptormedicine.medical_treatmentBiologyGyrus CinguliEpigenesis Genetic03 medical and health sciencesCellular and Molecular Neurosciencechemistry.chemical_compoundMice0302 clinical medicineReceptor Cannabinoid CB1Internal medicinemental disordersmedicineAnimalsHumansChronic stressNeuropeptide YPharmacologyHistone deacetylase 2URB597Endocannabinoid systemhumanitiesMice Inbred C57BL030104 developmental biologyEndocrinologychemistryBenzamidesCannabinoidHistone deacetylaseCarbamates030217 neurology & neurosurgeryStress PsychologicalNeuropharmacology
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Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice

2013

The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice recei…

Apolipoprotein Emedicine.medical_specialtyApolipoprotein BNeutrophilsPolyunsaturated Alkamidesmedicine.medical_treatmentIntraperitoneal injectionGene ExpressionArachidonic AcidsDiet High-FatAmidohydrolasesMicechemistry.chemical_compoundApolipoproteins EWestern blotCell MovementSuperoxidesFatty acid amide hydrolaseInternal medicinemedicineAnimalsEnzyme InhibitorsMolecular BiologyMice Knockoutbiologymedicine.diagnostic_testChemistryMacrophagesAnandamideURB597Dietary FatsEndocannabinoid systemPlaque AtheroscleroticEndocrinologyBenzamidesbiology.proteinCarbamatesCardiology and Cardiovascular MedicineEndocannabinoidsJournal of Molecular and Cellular Cardiology
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Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothal…

2015

Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamine…

AstrocitosNeurobiologia del desenvolupamentAmidohidrolasasCannabinoid receptorCarbamatos:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases [Medical Subject Headings]:Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::Neurogenesis [Medical Subject Headings]medicine.medical_treatment:Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings]Apoptosis:Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings]chemistry.chemical_compound:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Membrane Proteins::Receptors Cell Surface::Receptors G-Protein-Coupled::Receptors Cannabinoid::Receptor Cannabinoid CB1 [Medical Subject Headings]0302 clinical medicine:Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids Acyclic::Carbamates [Medical Subject Headings]Fatty acid amide hydrolaseReceptor cannabinoide CB1:Organisms::Eukaryota::Animals [Medical Subject Headings]FAAHGliosishealth care economics and organizations:Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine [Medical Subject Headings]:Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings]Original Research0303 health sciencesNeurogenesisBenzamidas:Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::Cholesterol [Medical Subject Headings]Endocannabinoid systemEtanolaminas3. Good healthEndocannabinoides:Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids Unsaturated::Fatty Acids Monounsaturated::Oleic Acids [Medical Subject Headings]CannabinoidesMicroglíalipids (amino acids peptides and proteins)medicine.symptomColesterol:Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids [Medical Subject Headings]:Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids [Medical Subject Headings]psychological phenomena and processesProliferación celularmedicine.medical_specialtyCerebroNeurogenesiseducationBiologyBromodesoxiuridina:Anatomy::Nervous System::Neuroglia::Microglia [Medical Subject Headings]Triglicéridoslcsh:RC321-571Ácidos oléicosRatas03 medical and health sciencesCellular and Molecular NeuroscienceInternal medicineHipocampomedicineCaspasa 3:Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus [Medical Subject Headings]:Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings]lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry030304 developmental biologyPalmitoylethanolamide:Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings]:Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases [Medical Subject Headings]Cannabinoids:Anatomy::Cells::Neuroglia::Astrocytes [Medical Subject Headings]Peso corporalEnergy metabolism:Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings]:Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus [Medical Subject Headings]URB597:Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death [Medical Subject Headings]:Diseases::Pathological Conditions Signs and Symptoms::Pathologic Processes::Gliosis [Medical Subject Headings]:Chemicals and Drugs::Organic Chemicals::Amines::Amino Alcohols::Ethanolamines [Medical Subject Headings]Muerte celular:Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings]:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings]EndocrinologyURB597chemistryGliosisnervous systemGlucosaCannabinoidEnergy Metabolism:Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings]HipotálamoÁcidos palmíticos030217 neurology & neurosurgeryNeuroscienceFrontiers in Cellular Neuroscience
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Evidence for a modulatory role of cannabinoids on the excitatory NANC neurotransmission in mouse colon

2007

Abstract It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinal motility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on a possible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission, the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation (EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal…

CB1 receptorIndolesCannabinoid receptormedicine.medical_treatmentSynaptic TransmissionSettore BIO/09 - FisiologiaEnteric Nervous SystemReceptor Cannabinoid CB2Micechemistry.chemical_compoundPiperidinesReceptor Cannabinoid CB1Fatty acid amide hydrolaseCannabinoid receptor type 2musculoskeletal neural and ocular physiologyAnandamideSmooth muscle contractionRimonabantAgonistmedicine.medical_specialtyColonPolyunsaturated Alkamidesmedicine.drug_classMorpholinesNeuromuscular JunctionArachidonic AcidsIn Vitro TechniquesNaphthalenesTachykininsInternal medicineCannabinoid Receptor ModulatorsIntestinal motilitymedicineAnimalsCannabinoidReceptors TachykininPharmacologyDose-Response Relationship DrugCannabinoidsExcitatory Postsynaptic PotentialsNANC relaxationURB597Electric StimulationBenzoxazinesMice Inbred C57BLEndocrinologyInhibitory Postsynaptic PotentialschemistryPyrazolesNANC contractionCannabinoidGastrointestinal MotilityEndocannabinoidsPharmacological Research
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Anti-inflammatory lipoxin A4 is an endogenous allosteric enhancer of CB1 cannabinoid receptor.

2012

Allosteric modulation of G-protein–coupled receptors represents a key goal of current pharmacology. In particular, endogenous allosteric modulators might represent important targets of interventions aimed at maximizing therapeutic efficacy and reducing side effects of drugs. Here we show that the anti-inflammatory lipid lipoxin A 4 is an endogenous allosteric enhancer of the CB 1 cannabinoid receptor. Lipoxin A 4 was detected in brain tissues, did not compete for the orthosteric binding site of the CB 1 receptor (vs. 3 H-SR141716A), and did not alter endocannabinoid metabolism (as opposed to URB597 and MAFP), but it enhanced affinity of anandamide at the CB1 receptor, thereby potentiating …

Cannabinoid receptorAllosteric regulationAnti-Inflammatory AgentsSpatial BehaviorEndogenyAmyloidogenic ProteinsMice TransgenicBiologyPharmacologyReceptors G-Protein-Coupled03 medical and health scienceschemistry.chemical_compoundMice0302 clinical medicineReceptor Cannabinoid CB1In vivoMemoryCommentariesAnimalsReceptor030304 developmental biologyInflammationMice Knockout0303 health sciencesMultidisciplinarymusculoskeletal neural and ocular physiologyBrainAnandamideURB597Biological SciencesEndocannabinoid system3. Good healthLipoxinsMice Inbred C57BLKineticsNeuroprotective Agentschemistrynervous systemlipids (amino acids peptides and proteins)030217 neurology & neurosurgerypsychological phenomena and processesAllosteric SiteEndocannabinoidsProceedings of the National Academy of Sciences of the United States of America
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The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synap…

2017

Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy. However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats. We found that both the fatty acid amide hydrolase (FAAH) inhibitor URB597 and the synthetic cannabinoid agonist WIN55,212-2 displayed AM…

Male0301 basic medicinemedicine.medical_treatmentLong-Term Potentiationlcsh:MedicineBrain -- Diseases -- DiagnosisSynaptic TransmissionEpilepsy -- Alternative treatmentchemistry.chemical_compoundEpilepsy0302 clinical medicineFatty acid amide hydrolaselcsh:ScienceTemporal lobe epilepsyInhibitionNeuronal PlasticityMultidisciplinaryLong-term potentiationmedicine.anatomical_structureAnesthesiaBenzamidesHippocampus (Brain)medicine.medical_specialtyArticleAmidohydrolases03 medical and health sciencesSeizuresInternal medicinemedicineAnimalsAuthor CorrectionEpilepsyCannabinoidsDentate gyruslcsh:RURB597medicine.diseaseGranule cellHippocampus (Brain) -- PhysiologyRats030104 developmental biologyEndocrinologychemistryDentate GyrusSynaptic plasticitylcsh:QNeuroplasticityCarbamatesCannabinoid030217 neurology & neurosurgery
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Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

2014

The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We…

MaleAnxietyPharmacologyAmidohydrolaseschemistry.chemical_compoundPiperidinesFatty acid amide hydrolaseNerve Growth FactorAnimalsMedicineChronic stressBenzodioxolesEnzyme InhibitorsJZL184PharmacologyDepressionbusiness.industryUncertaintyChronic painBrainAnalgesics Non-NarcoticURB597medicine.diseaseEndocannabinoid systemMonoacylglycerol LipasesMice Inbred C57BLDisease Models AnimalPsychiatry and Mental healthNociceptionchemistryHyperalgesiaAnesthesiaBenzamidesHyperalgesiaOriginal ArticleCarbamatesChronic Painmedicine.symptombusinessStress PsychologicalEndocannabinoidsNeuropsychopharmacology
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Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (…

2007

Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects in rodents. The present study adopted both genetic and pharmacological approaches and tested the hypothesis that FAAH-deficient…

MaleCannabinoid receptorPolyunsaturated Alkamidesmedicine.medical_treatmentArachidonic AcidsAnxietyPharmacologyAmidohydrolasesGlyceridesMiceCellular and Molecular Neurosciencechemistry.chemical_compoundPiperidinesReceptor Cannabinoid CB1RimonabantFatty acid amide hydrolaseCannabinoid receptor type 1medicineAnimalsMaze LearningMice KnockoutPharmacologyAnalysis of VarianceBehavior AnimalAnandamideURB597Endocannabinoid systemMice Inbred C57BLDisease Models Animalnervous systemchemistryBenzamidesPyrazoleslipids (amino acids peptides and proteins)CarbamatesCannabinoidRimonabantpsychological phenomena and processesEndocannabinoidsmedicine.drugNeuropharmacology
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Endocannabinoid anandamide mediates hypoxic pulmonary vasoconstriction

2013

Endocannabinoids are important regulators of organ homeostasis. Although their role in systemic vasculature has been extensively studied, their impact on pulmonary vessels remains less clear. Herein, we show that the endocannabinoid anandamide (AEA) is a key mediator of hypoxic pulmonary vasoconstriction (HPV) via fatty acid amide hydrolase (FAAH)-dependent metabolites. This is underscored by the prominent vasoconstrictive effect of AEA on pulmonary arteries and strongly reduced HPV in FAAH(-/-) mice and wild-type mice upon pharmacological treatment with FAAH inhibitor URB597. In addition, mass spectrometry measurements revealed a clear increase of AEA and the FAAH-dependent metabolite arac…

medicine.medical_specialtyPolyunsaturated Alkamidesmedicine.medical_treatmentHypertension PulmonaryBlotting WesternMyocytes Smooth MuscleArachidonic AcidsBiologyAmidohydrolaseschemistry.chemical_compoundMiceFatty acid amide hydrolaseInternal medicineHypoxic pulmonary vasoconstrictionmedicineAnimalsHypoxiaLungDNA PrimersMice KnockoutAnalysis of VarianceMultidisciplinaryReverse Transcriptase Polymerase Chain ReactionAnandamideHypoxia (medical)URB597Biological Sciencesmedicine.diseaseEndocannabinoid systemPulmonary hypertensionImmunohistochemistryEndocrinologynervous systemchemistryVasoconstrictionBenzamideslipids (amino acids peptides and proteins)CannabinoidCarbamatesmedicine.symptompsychological phenomena and processesChromatography LiquidEndocannabinoidsSignal Transduction
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