2014
Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors
McClure-Begley TD, Papke RL, Stone KL, Stokes C, Levy AD, Gelernter J, Xie P, Lindstrom J, Picciotto MR. Rare Human Nicotinic Acetylcholine Receptor α4 Subunit (CHRNA4) Variants Affect Expression and Function of High-Affinity Nicotinic Acetylcholine Receptors. Journal Of Pharmacology And Experimental Therapeutics 2014, 348: 410-420. PMID: 24385388, PMCID: PMC3935145, DOI: 10.1124/jpet.113.209767.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBridged Bicyclo Compounds, HeterocyclicCell MembraneFemaleHEK293 CellsHumansNicotineNicotinic AgonistsOocytesPhosphorylationPolymorphism, GeneticProtein SubunitsPyridinesReceptors, NicotinicUp-RegulationXenopus laevisConceptsNicotinic acetylcholine receptorsRare variantsSingle amino acid substitutionLaevis oocytesAmino acid substitutionsΑ4β2 nAChRsAcetylcholine receptorsIntracellular interactomesHEK-293 cellsX. laevis oocytesProteomic analysisGenetic variationHuman α4β2 nAChRsXenopus laevis oocytesVoltage-clamp electrophysiologyNeuronal nicotinic acetylcholine receptorsHigh-affinity nicotinic acetylcholine receptorsSubcellular distributionAcid substitutionsΑ4 nAChR subunitCohort of smokersEffects of nicotineNAChR subunitsCommon variantsΑ4 nAChR
2013
Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule
Peng C, Stokes C, Mineur YS, Picciotto MR, Tian C, Eibl C, Tomassoli I, Guendisch D, Papke RL. Differential Modulation of Brain Nicotinic Acetylcholine Receptor Function by Cytisine, Varenicline, and Two Novel Bispidine Compounds: Emergent Properties of a Hybrid Molecule. Journal Of Pharmacology And Experimental Therapeutics 2013, 347: 424-437. PMID: 23959137, PMCID: PMC3807070, DOI: 10.1124/jpet.113.206904.Peer-Reviewed Original ResearchMeSH KeywordsAlkaloidsAnimalsAzocinesBehavior, AnimalBenzazepinesBrainBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Partial AgonismHEK293 CellsHumansMaleMembrane PotentialsMiceMolecular StructureNicotinic AgonistsOocytesPatch-Clamp TechniquesQuinolizinesQuinoxalinesRatsRats, Sprague-DawleyReceptors, NicotinicTobacco Use DisorderVareniclineXenopus laevisConceptsPartial agonistLGN neuronsMouse tail suspension testLateral geniculate nucleus neuronsNicotinic acetylcholine receptor functionPartial agonist therapiesTail suspension testStratum radiatum interneuronsSmoking cessation drugNicotinic partial agonistAcetylcholine receptor functionHuman embryonic kidney 293 cellsSteady-state activationAgonist therapyRadiatum interneuronsEmbryonic kidney 293 cellsCessation drugsNucleus neuronsSuspension testΑ7 currentsNicotine addictionSide effectsVareniclineΑ4β2 nAChRsSR interneuronsNicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex
Yang Y, Paspalas CD, Jin LE, Picciotto MR, Arnsten AF, Wang M. Nicotinic α7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 12078-12083. PMID: 23818597, PMCID: PMC3718126, DOI: 10.1073/pnas.1307849110.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAconitineAlpha7 Nicotinic Acetylcholine ReceptorAnalysis of VarianceAnimalsBridged Bicyclo Compounds, HeterocyclicCholinergic AgonistsCholinergic AntagonistsCognitionFemaleIontophoresisMacaca mulattaMaleMecamylamineMicroscopy, ImmunoelectronN-MethylaspartatePhenolsPiperidinesPrefrontal CortexQuinuclidinesReceptors, NicotinicSpatial BehaviorSynapsesVisual PerceptionConceptsDorsolateral prefrontal cortexΑ7 nAChRsPrefrontal cortexΑ7 nicotinic acetylcholine receptorGlutamatergic NMDA receptorsCognitive circuitsNicotinic α7 receptorsPrimary visual cortexNMDA receptor actionGenetic insultsNicotinic acetylcholine receptorsDlPFC circuitsPrimate dlPFCACh depletionNMDA actionNMDA receptorsPyramidal cellsΑ7 receptorsNeuronal firingNAChR blockadeAcetylcholine receptorsVisual cortexPersistent firingCognitive functionLow-dose stimulation
2011
Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD
Wigestrand MB, Mineur YS, Heath CJ, Fonnum F, Picciotto MR, Walaas SI. Decreased α4β2 nicotinic receptor number in the absence of mRNA changes suggests post‐transcriptional regulation in the spontaneously hypertensive rat model of ADHD. Journal Of Neurochemistry 2011, 119: 240-250. PMID: 21824140, PMCID: PMC3171636, DOI: 10.1111/j.1471-4159.2011.07415.x.Peer-Reviewed Original ResearchMeSH KeywordsAconitineAnimalsAttention Deficit Disorder with HyperactivityAzetidinesBrain ChemistryBridged Bicyclo Compounds, HeterocyclicBungarotoxinsIn Vitro TechniquesKineticsMaleMembranesNicotinic AgonistsNicotinic AntagonistsProtein Processing, Post-TranslationalPyridinesRatsRats, Inbred SHRRats, Inbred WKYReceptors, NicotinicReverse Transcriptase Polymerase Chain ReactionRNA, MessengerThermodynamicsConceptsAttention-deficit/hyperactivity disorderQuantitative real-time PCRBrain regionsCerebellum of SHRWistar-Kyoto rat controlsHypertensive rat modelMRNA levelsNicotinic receptor numbersCentral nicotinic receptorsSpecific brain regionsAdditional brain regionsSHR brainHypertensive ratsRat modelReal-time PCRNicotinic receptorsReceptor numberEpidemiological studiesLevels of mRNAΑ4β2 nAChRsSHRWKYNAChRsHyperactivity disorderStrain differences
2002
Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice
Marks MJ, Whiteaker P, Grady SR, Picciotto MR, McIntosh JM, Collins AC. Characterization of [125I]epibatidine binding and nicotinic agonist‐mediated 86Rb+ efflux in interpeduncular nucleus and inferior colliculus of β2 null mutant mice. Journal Of Neurochemistry 2002, 81: 1102-1115. PMID: 12065623, DOI: 10.1046/j.1471-4159.2002.00910.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetylcholineAlkaloidsAnimalsAzocinesBinding, CompetitiveBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugInferior ColliculiIodine RadioisotopesMesencephalonMiceMice, Mutant StrainsNicotinic AgonistsNicotinic AntagonistsPyridinesQuinolizinesReceptors, NicotinicRubidium RadioisotopesTritiumConceptsInterpeduncular nucleusInferior colliculusBrain regionsAccessory olfactory nucleusNull mutant miceOlfactory nucleusNicotinic antagonistsD-tubocurarineMedial habenulaSelective antagonistNicotinic agonistsSuperior colliculusMouse brainAgonistsColliculusMutant micePotent agonistSimilar potencyAntagonistNicotinic activityEfflux
2000
Nicotinic-agonist stimulated 86Rb+ efflux and [3H]epibatidine binding of mice differing in β2 genotype
Marks M, Stitzel J, Grady S, Picciotto M, Changeux J, Collins A. Nicotinic-agonist stimulated 86Rb+ efflux and [3H]epibatidine binding of mice differing in β2 genotype. Neuropharmacology 2000, 39: 2632-2645. PMID: 11044733, DOI: 10.1016/s0028-3908(00)00115-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBridged Bicyclo Compounds, HeterocyclicBungarotoxinsFemaleGenotypeKineticsMaleMiceNicotinic AgonistsPotassiumPyridinesReceptors, NicotinicRubidiumRubidium RadioisotopesStimulation, ChemicalVeratridineConceptsBrain regionsNicotinic acetylcholine receptor functionBeta2 subunitBeta2-containing receptorsAcetylcholine receptor functionHigh-affinity siteBeta2 subunit expressionBinding of mouseCerebral cortexNicotinic responsesMicroM nicotineOlfactory bulbInferior colliculusNicotinic agonistsSubunit expressionReceptor functionLow affinityLow affinity sitesDHbetaEInhibitionMiceStimulationEffluxCytisineNull mutationPharmacological and null mutation approaches reveal nicotinic receptor diversity
Whiteaker P, Marks M, Grady S, Lu Y, Picciotto M, Changeux J, Collins A. Pharmacological and null mutation approaches reveal nicotinic receptor diversity. European Journal Of Pharmacology 2000, 393: 123-135. PMID: 10771005, DOI: 10.1016/s0014-2999(00)00052-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAutoradiographyBrainBridged Bicyclo Compounds, HeterocyclicCell MembraneGenetic VariationGenotypeMiceMice, Inbred C57BLMutationNicotinic AgonistsPyridinesReceptors, NicotinicSynaptosomesTritiumConceptsNicotinic acetylcholine receptor functionNicotinic acetylcholine receptorsAcetylcholine receptor functionAcetylcholine receptorsNicotinic acetylcholine receptor bindingReceptor functionNative nicotinic acetylcholine receptorsNicotinic acetylcholine receptor subtypesWhole brain preparationAcetylcholine receptor bindingAcetylcholine receptor subtypesMouse brain membranesArray of assaysReceptor subtypesPharmacological comparisonComparative pharmacologyBrain nucleiBrain membranesEfflux techniqueReceptor bindingSubunit deletionReceptor diversityReceptorsAminobutyric acidSubtypes