2025
The polypharmacology of psychedelics reveals multiple targets for potential therapeutics
Jain M, Gumpper R, Slocum S, Schmitz G, Madsen J, Tummino T, Suomivuori C, Huang X, Shub L, DiBerto J, Kim K, DeLeon C, Krumm B, Fay J, Keiser M, Hauser A, Dror R, Shoichet B, Gloriam D, Nichols D, Roth B. The polypharmacology of psychedelics reveals multiple targets for potential therapeutics. Neuron 2025 PMID: 40683247, DOI: 10.1016/j.neuron.2025.06.012.Peer-Reviewed Original ResearchPost-traumatic stress disorderAction of psychedelicsStress disorderPsychedelic effectsNeuropsychiatric conditionsSerotonin receptorsAcid diethylamidePsychedelicsDrug abuseCase of LSDG protein-coupled receptorsAdrenergic receptorsAction in vivoCluster headacheLSDClinical studiesPsilocybinSerotoninDopamineTherapeutic potentialAnxietyMescalineDiethylamideEfficacious actionDepression
2023
Alpha-1 Adrenergic Antagonists Sensitize Neuroblastoma to Therapeutic Differentiation.
Broso F, Gatto P, Sidarovich V, Ambrosini C, De Sanctis V, Bertorelli R, Zaccheroni E, Ricci B, Destefanis E, Longhi S, Sebastiani E, Tebaldi T, Adami V, Quattrone A. Alpha-1 Adrenergic Antagonists Sensitize Neuroblastoma to Therapeutic Differentiation. Cancer Research 2023, 83: 2733-2749. PMID: 37289021, DOI: 10.1158/0008-5472.can-22-1913.Peer-Reviewed Original ResearchConceptsResidual diseaseAdrenergic antagonistsAdrenergic receptorsAlpha-1 adrenergic antagonistAdministration of doxazosinPost-consolidation therapyOverall survival probabilityPrevention of relapseHigh-risk casesMultimodal therapeutic approachPost-consolidation phaseDifferentiation of neuroblastomaNB cell viabilityAggressive childhood tumorRetinoids isotretinoinPediatric patientsΑ1B-adrenergic receptorPrevent relapseChildhood tumorsTherapeutic approachesSpecific blockadeNB cellsPharmacologic targetNeuroblastomaTumor growthAdrenergic receptors regulate T cell differentiation in viral infection and cancer
Globig A, Zhao S, Roginsky J, Avina-Ochoa N, Heeg M, Chaudhary O, Hoffmann F, Chen D, O’Connor C, Emu B, Kaech S. Adrenergic receptors regulate T cell differentiation in viral infection and cancer. The Journal Of Immunology 2023, 210: 59.13-59.13. DOI: 10.4049/jimmunol.210.supp.59.13.Peer-Reviewed Original ResearchImmune checkpoint blockadeT cell differentiationChronic viral infectionsT cell functionalityT cellsViral infectionAdrenergic receptorsChronic antigen exposureLCMV clone 13Novel immune checkpointT cell proliferationMurine cancer modelsT cell receptor signalingCell differentiationAbstract CD8Terminal-CD8Exhausted CD8Checkpoint blockadeAntigen exposureImmune checkpointsNoradrenaline levelsCell receptor signalingTumor sizeCancer patientsNA receptorsIncreased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy
Rupert C, López J, Cortez-Toledo E, De la Cruz Cabrera O, Chesler N, Simpson P, Campbell S, Baker A. Increased length-dependent activation of human engineered heart tissue after chronic α1A-adrenergic agonist treatment: testing a novel heart failure therapy. AJP Heart And Circulatory Physiology 2023, 324: h293-h304. PMID: 36637971, PMCID: PMC9886349, DOI: 10.1152/ajpheart.00279.2022.Peer-Reviewed Original ResearchConceptsHuman heart failureHeart failureAR stimulationChronic stimulationLength-dependent activationVehicle treatmentHeart tissueAdrenergic receptorsHuman EHTsAnimal heart failure modelNovel heart failure therapiesHeart failure therapyHeart failure modelMultiple preclinical modelsFailure therapyAgonist treatmentSeparate control experimentsPreclinical modelsDrug washoutTherapeutic effectTranslational significanceHuman myocardiumBaseline testingRNA-seq analysisPig myocardium
2020
Loss of p53 drives neuron reprogramming in head and neck cancer
Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020, 578: 449-454. PMID: 32051587, PMCID: PMC9723538, DOI: 10.1038/s41586-020-1996-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AntagonistsAdrenergic NeuronsAnimalsCell DivisionCell TransdifferentiationCellular ReprogrammingDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiceMice, Inbred BALB CMicroRNAsMouth NeoplasmsNerve FibersNeuritesReceptors, AdrenergicRetrospective StudiesSensory Receptor CellsTumor MicroenvironmentTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOral cancerNerve fibersAdrenergic nerve fibersPoor clinical outcomeTrigeminal sensory neuronsLoss of TP53Sensory denervationAdrenergic nervesChemical sympathectomyNerve densitySensory nervesClinical outcomesSolid tumor microenvironmentLoss of p53Neck cancerPharmacological blockadeEndogenous neuronsRetrospective analysisMouse modelSensory neuronsAdrenergic phenotypeAdrenergic receptorsTumor growthTumor progressionTumor microenvironment
2019
Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask)
Schena G, Caplan MJ. Everything You Always Wanted to Know about β3-AR * (* But Were Afraid to Ask). Cells 2019, 8: 357. PMID: 30995798, PMCID: PMC6523418, DOI: 10.3390/cells8040357.Peer-Reviewed Original ResearchConceptsNovel pharmacological approachesCurrent clinical practiceNovel therapeutic targetAR signalingΒ3-ARPharmacological approachesOcular diseasesTherapeutic targetAdrenergic receptorsClinical practiceFindings translateClinical areasCellular modelSuitable animalAppealing targetInter-species differencesDiseaseReceptors
2018
Phosphoproteomic Analysis of the Amygdala Response to Adolescent Glucocorticoid Exposure Reveals G-Protein Coupled Receptor Kinase 2 as a Target for Reducing Motivation for Alcohol
Bertholomey ML, Stone K, Lam TT, Bang S, Wu W, Nairn AC, Taylor JR, Torregrossa MM. Phosphoproteomic Analysis of the Amygdala Response to Adolescent Glucocorticoid Exposure Reveals G-Protein Coupled Receptor Kinase 2 as a Target for Reducing Motivation for Alcohol. Proteomes 2018, 6: 41. PMID: 30322021, PMCID: PMC6313880, DOI: 10.3390/proteomes6040041.Peer-Reviewed Original ResearchAlcohol use disorderReceptor kinase 2CORT exposureG-Protein Coupled Receptor Kinase 2AR antagonist yohimbineAdolescent stress exposureStress-induced reinstatementAlcohol-motivated behaviorsEarly life stressIntra-amygdala infusionPotential novel mechanismAntagonist yohimbineGlucocorticoid exposureKinase 2Alcohol drinkingCorticosterone exposureLong-term consequencesUse disordersElevated glucocorticoidsGRK2 inhibitorAdrenergic receptorsChronic exposureReinstatement testBrain functionNovel targetα1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice
Zhang H, Chaudhury D, Nectow AR, Friedman AK, Zhang S, Juarez B, Liu H, Pfau ML, Aleyasin H, Jiang C, Crumiller M, Calipari ES, Ku SM, Morel C, Tzavaras N, Montgomery SE, He M, Salton SR, Russo SJ, Nestler EJ, Friedman JM, Cao JL, Han MH. α1- and β3-Adrenergic Receptor–Mediated Mesolimbic Homeostatic Plasticity Confers Resilience to Social Stress in Susceptible Mice. Biological Psychiatry 2018, 85: 226-236. PMID: 30336931, PMCID: PMC6800029, DOI: 10.1016/j.biopsych.2018.08.020.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-1 Receptor AgonistsAdrenergic alpha-1 Receptor AntagonistsAdrenergic beta-3 Receptor AgonistsAdrenergic beta-3 Receptor AntagonistsAnimalsBehavior, AnimalDopaminergic NeuronsHomeostasisLocus CoeruleusMaleMiceNeural PathwaysNeuronal PlasticityReceptors, Adrenergic, alpha-1Receptors, Adrenergic, beta-3Resilience, PsychologicalStress, PsychologicalVentral Tegmental AreaConceptsSocial defeat stressDA neuronsSusceptible miceHomeostatic plasticityLocus coeruleusDefeat stressAdrenergic receptorsChronic social defeat stress (CSDS) modelSocial defeat stress modelVTA DA neuronsDepression-related behaviorsMesolimbic DA neuronsMesolimbic dopamine neuronsΒ3-adrenergic receptorMolecular profiling studiesNew molecular targetsSocial stressCircuit neuronsLC neuronsDopamine neuronsNucleus accumbensOptogenetic activationCellular hyperactivityPrecise circuitryStress resilienceDorsal BNST α2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors
Harris NA, Isaac AT, Günther A, Merkel K, Melchior J, Xu M, Eguakun E, Perez R, Nabit BP, Flavin S, Gilsbach R, Shonesy B, Hein L, Abel T, Baumann A, Matthews R, Centanni SW, Winder DG. Dorsal BNST α2A-Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors. Journal Of Neuroscience 2018, 38: 8922-8942. PMID: 30150361, PMCID: PMC6191524, DOI: 10.1523/jneurosci.0963-18.2018.Peer-Reviewed Original ResearchConceptsExcitatory actionAnxiety-like behaviorBed nucleusNeuronal activityAdrenergic receptorsCation channelsEffective treatment modalityDorsal bed nucleusHyperpolarization-activated cyclicCell-specific actionsSubstance use disordersReward-related behaviorsDrug-seeking behaviorDrugs of abuseTreatment of addictionAntidepressant actionBNST neuronsAnxiolytic actionDorsal BNSTTreatment modalitiesReceptor agonistAgonist guanfacineAnxiogenic behaviorStria terminalisClinical utility
2017
Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers
Polimanti R, Kaufman J, Zhao H, Kranzler HR, Ursano RJ, Kessler RC, Stein MB, Gelernter J. Trauma exposure interacts with the genetic risk of bipolar disorder in alcohol misuse of US soldiers. Acta Psychiatrica Scandinavica 2017, 137: 148-156. PMID: 29230810, PMCID: PMC6110087, DOI: 10.1111/acps.12843.Peer-Reviewed Original ResearchConceptsBD polygenic risk scorePolygenic risk scoresAlcohol misuseBipolar disorderTrauma exposurePsychiatric disordersGenetic riskMajor depressive disorderNicotine dependence symptomsSubstance use disordersSchizophrenia polygenic risk scoresVoltage-gated calcium channel activityCalcium channel activityUS Army soldiersBeta2-adrenergic receptorDepressive disorderRisk scoreUse disordersAdrenergic receptorsMental disordersSubstance abuseDisordersDependence symptomsChannel activityExposureAdrenergic nerves activate an angio-metabolic switch in prostate cancer
Zahalka AH, Arnal-Estapé A, Maryanovich M, Nakahara F, Cruz CD, Finley LWS, Frenette PS. Adrenergic nerves activate an angio-metabolic switch in prostate cancer. Science 2017, 358: 321-326. PMID: 29051371, PMCID: PMC5783182, DOI: 10.1126/science.aah5072.Peer-Reviewed Original ResearchMeSH KeywordsAlkyl and Aryl TransferasesAnimalsCarrier ProteinsElectron Transport Complex IVEndothelium, VascularGene DeletionHumansMaleMembrane ProteinsMiceMitochondrial ProteinsNeovascularization, PathologicNerve FibersNorepinephrineOxidative PhosphorylationProstateProstatic NeoplasmsReceptors, Adrenergic, beta-2Signal TransductionTumor Microenvironment
2014
Function and dynamics of macromolecular complexes explored by integrative structural and computational biology
Purdy M, Bennett B, McIntire W, Khan A, Kasson P, Yeager M. Function and dynamics of macromolecular complexes explored by integrative structural and computational biology. Current Opinion In Structural Biology 2014, 27: 138-148. PMID: 25238653, PMCID: PMC6387792, DOI: 10.1016/j.sbi.2014.08.006.Peer-Reviewed Original ResearchConceptsMacromolecular complexesX-ray crystallographyIntegrative structural biologyG protein complexProtein complexesStructural biologyMD simulationsMicrosecond MD simulationsFunctional dynamicsX-ray crystallographic dataMolecular dynamics simulationsComputational biologyBiologyNew insightsBiological systemsCrystallographic dataUnprecedented synergyDynamics simulationsCrystallographyComplexesFunctional propertiesRibosomesTransmembraneGPCRsAdrenergic receptors
2013
Homotypic and Heterotypic Adhesion Induced by Odorant Receptors and the β2-Adrenergic Receptor
Richard M, Jamet S, Fouquet C, Dubacq C, Boggetto N, Pincet F, Gourier C, Trembleau A. Homotypic and Heterotypic Adhesion Induced by Odorant Receptors and the β2-Adrenergic Receptor. PLOS ONE 2013, 8: e80100. PMID: 24312457, PMCID: PMC3846556, DOI: 10.1371/journal.pone.0080100.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsΒ2-adrenergic receptorOlfactory axonsAxon sortingOlfactory sensory neuron projectionsSensory neuron projectionsSubpopulation of axonsMouse olfactory systemOdorant receptorsProtein-coupled receptorsHeterotypic adhesionSensory neuronsAdrenergic receptorsAxonal wiringNeuron projectionsAxonsReceptorsOlfactory systemMOR256-17First evidenceCritical determinant
2012
An environmental epigenetic study of ADRB2 5′‐UTR methylation and childhood asthma severity
Fu A, Leaderer BP, Gent JF, Leaderer D, Zhu Y. An environmental epigenetic study of ADRB2 5′‐UTR methylation and childhood asthma severity. Clinical & Experimental Allergy 2012, 42: 1575-1581. PMID: 22862293, PMCID: PMC3673701, DOI: 10.1111/j.1365-2222.2012.04055.x.Peer-Reviewed Original ResearchConceptsChildhood asthma severityAsthma severitySevere asthmaSignificant associationSevere childhood asthmaBeta-agonist treatmentBeta-2 adrenergic receptorsImportant environmental exposuresAsthma exacerbationsAsthma medicationsMild asthmaChildhood asthmaSurrogate biomarkerMethylation-specific PCRPotential joint effectsClinical relevanceAdrenergic receptorsAsthmaADRB2SeverityEnvironmental exposuresIndoor exposureChildrenAssociationBloodTobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses
Alexandre M, Uduman AK, Minervini S, Raoof A, Shugrue CA, Akinbiyi EO, Patel V, Shitia M, Kolodecik TR, Patton R, Gorelick FS, Thrower EC. Tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone initiates and enhances pancreatitis responses. AJP Gastrointestinal And Liver Physiology 2012, 303: g696-g704. PMID: 22837343, PMCID: PMC3468532, DOI: 10.1152/ajpgi.00138.2012.Peer-Reviewed Original ResearchConceptsNicotinic acetylcholine receptorsAcetylcholine receptorsCigarette smoke toxinsParameters of pancreatitisPancreatitis responsesTobacco carcinogen 4Acinar cell responsesRat pancreatic aciniSmoke toxinsAcute pancreatitisCigarette smokingIntraperitoneal injectionAcinar cell preparationsClinical studiesLong-term effectsCarcinogen 4Pancreatitis modelAdrenergic receptorsReceptor typesCell responsesTobacco toxinsPyknotic nucleiNNKPancreatic aciniPancreatitis
2011
Amyloid β Peptide-(1–42) Induces Internalization and Degradation of β2 Adrenergic Receptors in Prefrontal Cortical Neurons*
Wang D, Yuen E, Zhou Y, Yan Z, Xiang Y. Amyloid β Peptide-(1–42) Induces Internalization and Degradation of β2 Adrenergic Receptors in Prefrontal Cortical Neurons*. Journal Of Biological Chemistry 2011, 286: 31852-31863. PMID: 21757762, PMCID: PMC3173113, DOI: 10.1074/jbc.m111.244335.Peer-Reviewed Original ResearchConceptsPrefrontal cortical neuronsCortical neuronsAdrenergic receptorsAMPA receptor-mediated miniature excitatory postsynaptic currentsG protein-coupled receptor kinase phosphorylationMiniature excitatory postsynaptic currentsCerebrum of miceΒAR agonist isoproterenolAmyloid precursor protein geneExcitatory postsynaptic currentsG protein-coupled receptor kinasesPrecursor protein geneProtein-coupled receptor kinasesReceptor subunit 1Mutant presenilin 1Receptor kinase phosphorylationGlutamatergic activityGlutamatergic regulationAβ bindsInduces desensitizationAβ treatmentPostsynaptic currentsΒ2-adrenergic receptorSynaptic activityAgonist isoproterenol
2009
Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling
Joiner M, Lisé M, Yuen E, Kam A, Zhang M, Hall D, Malik Z, Qian H, Chen Y, Ulrich J, Burette A, Weinberg R, Law P, El‐Husseini A, Yan Z, Hell J. Assembly of a β2‐adrenergic receptor—GluR1 signalling complex for localized cAMP signalling. The EMBO Journal 2009, 29: 482-495. PMID: 19942860, PMCID: PMC2824466, DOI: 10.1038/emboj.2009.344.Peer-Reviewed Original ResearchMeSH KeywordsAdenylyl CyclasesAnimalsCalcium ChannelsCells, CulturedCerebral CortexCyclic AMP-Dependent Protein KinasesDisks Large Homolog 4 ProteinElectrophysiologyGene Expression RegulationGTP-Binding Protein alpha Subunits, GsHippocampusIntracellular Signaling Peptides and ProteinsMembrane ProteinsNeuronsRatsRats, Sprague-DawleyReceptors, Adrenergic, beta-2Receptors, AMPAConceptsUnknown molecular mechanismsMajor target proteinGluR1 surface expressionLocalized cAMPTarget proteinsMolecular mechanismsPhosphorylation of GluR1Selective regulationAdenylyl cyclaseProteinPSD-95PhosphorylationSurface expressionGlutamate receptor subunits GluR1PKAAssemblyPostsynaptic sitesCentral noradrenergic signalingHomologuesSubunit GluR1ComplexesCAMPSignalingAdrenergic receptorsStargazin
2006
β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension
Pojoga L, Kolatkar NS, Williams JS, Perlstein TS, Jeunemaitre X, Brown NJ, Hopkins PN, Raby BA, Williams GH. β-2 Adrenergic Receptor Diplotype Defines a Subset of Salt-Sensitive Hypertension. Hypertension 2006, 48: 892-900. PMID: 17015767, DOI: 10.1161/01.hyp.0000244688.45472.95.Peer-Reviewed Original ResearchConceptsBlood pressure responseSalt-sensitive hypertensionBeta-2 adrenergic receptorsAldosterone secretionDietary sodiumAdrenergic receptorsGreater blood pressure responseAdrenergic receptor variantsHigh plasma aldosteroneLow plasma reninLow-sodium balanceNormotensive white subjectsMean arterial pressureLow-renin hypertensionSerum potassium levelsAdrenergic receptor genotypePressure responseBlood pressure evaluationAdrenergic receptor stimulationAldosterone responseAldosterone systemHypertensive subjectsNormotensive subjectsPlasma aldosteronePlasma renin
2005
29 Blocking the Axonal Injury Cascade Neuroprotection in Multiple Sclerosis and Its Models
Waxman S, Lo A. 29 Blocking the Axonal Injury Cascade Neuroprotection in Multiple Sclerosis and Its Models. 2005, 435-449. DOI: 10.1016/b978-012738761-1/50030-4.Peer-Reviewed Original ResearchExperimental autoimmune encephalomyelitisWhite matter injuryAxonal injuryChannel blockersNitric oxideNon-glucocorticoid steroidsCalcium channel blockersHuman multiple sclerosis lesionsSodium channel blockersMultiple sclerosis lesionsEffects of drugsAutoimmune encephalomyelitisMS pathologyOptic nerveMultiple sclerosisFunctional outcomeNeuroprotective agentsΓ-aminobutyric acidHypoxic injuryPathological evidenceSpinal nervesSpinal cordAdrenergic receptorsVivo preparationSclerosis lesions
2000
Effects of Labetalol Treatment on the Physiological and Subjective Response to Smoked Cocaine
Sofuoglu M, Brown S, Babb D, Pentel P, Hatsukami D. Effects of Labetalol Treatment on the Physiological and Subjective Response to Smoked Cocaine. Pharmacology Biochemistry And Behavior 2000, 65: 255-259. PMID: 10672977, DOI: 10.1016/s0091-3057(99)00201-4.Peer-Reviewed Original ResearchConceptsSystolic blood pressureLabetalol treatmentBlood pressureDose of labetalolEffects of labetalolSubjective responsesCocaine deliveryHeart rate increaseCocaine-induced increasesEffect of treatmentCrossover studyMedication treatmentCardiovascular responsesHeart rateAdrenergic receptorsLabetalolSmoked CocaineBehavioral effectsSubjective effectsCocaineDrug labetalolCocaine usersTreatmentDosesExperimental sessions
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