Functional Neurokinin and NMDA Receptor Activity in an Animal Naturally Lacking Substance P The Naked Mole-Rat 英文参考文献.docVIP

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Functional Neurokinin and NMDA Receptor Activity in an Animal Naturally Lacking Substance P The Naked Mole-Rat 英文参考文献.doc

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Functional Neurokinin and NMDA Receptor Activity in an Animal Naturally Lacking Substance P The Naked Mole-Rat 英文参考文献

FunctionalNeurokininandNMDAReceptorActivityinan AnimalNaturallyLackingSubstanceP:TheNakedMole- Rat AntjeBrand1,EwanSt.J.Smith2,GaryR.Lewin2,ThomasJ.Park1* 1LaboratoryofIntegrativeNeuroscience,DepartmentofBiologicalSciences,UniversityofIllinoisatChicago,Chicago,Illinois,UnitedStatesofAmerica,2Departmentof Neuroscience,Max-Delbru¨ckCenterforMolecularMedicine,Berlin,Germany Abstract Nakedmole-ratsareextremelyunusualamongmammalsinthattheircutaneousC-fiberslacktheneuropeptideSubstanceP (SP).Inothermammals,SPplaysanimportantroleinnociception:itisreleasedfromC-fibersontospinalneuronswhereit facilitatesNMDAreceptoractivityandcausessensitizationthatcanlastforminutes,hoursordays.Inthepresentstudy,we testedtheeffectsofintrathecalapplicationof:1)SP,2)anSPantagonist(GR-82334),and3)anNMDAantagonist(APV)on heat-evoked foot withdrawal. In the naked mole-rat, at a high enough concentration, application of SP caused a large, immediate,andlong-lastingsensitizationoffootwithdrawallatencythatwastransientlyreversedbyapplicationofeither antagonist.However,neitherSPnorNMDAantagonistshadaneffectwhenadministeredalonetona?¨veanimals.Incontrast, both antagonists induced an increase in basal withdrawal latency in mice. These results indicate that spinal neurons in nakedmole-ratshavefunctionalSPandNMDAreceptors,butthatthesereceptorsdonotparticipateinheat-evokedfoot withdrawalunlessSPisexperimentallyintroduced.WeproposethatthenaturallackofSPinnakedmole-ratC-fibersmay haveresultedduringadaptationtolivinginachronicallyhighcarbondioxide,highammoniaenvironmentthat,inother mammals,wouldstimulateC-fibersandevokenocifensivebehavior. Citation:BrandA,SmithESJ,LewinGR,ParkTJ(2010)FunctionalNeurokininandNMDAReceptorActivityinanAnimalNaturallyLackingSubstanceP:TheNaked Mole-Rat.PLoSONE5(12):e15162.doi:10.1371/journal.pone.0015162 Editor:IvanIzquierdo,PontificalCatholicUniversityofRioGrande,Brazil ReceivedSeptember20,2010;AcceptedOctober26,2010;PublishedDecember21,2010 Copyright: ? 2010 Brand et al. This is