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Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier relevance to neural disorders 英文参考文献.docVIP

Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier relevance to neural disorders 英文参考文献.doc

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Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier relevance to neural disorders 英文参考文献

FLUIDS AND BARRIERS OF THE CNS Transportcharacteristicsofguanidinocompoundsat theblood-brainbarrierandblood-cerebrospinalfluid barrier:relevancetoneuraldisorders TachikawaandHosoya TachikawaandHosoyaFluidsandBarriersoftheCNS2011,8:13 /content/8/1/13(28February2011) TachikawaandHosoyaFluidsandBarriersoftheCNS2011,8:13 /content/8/1/13 FLUIDS AND BARRIERS OF THE CNS REVIEW OpenAccess Transportcharacteristicsofguanidinocompounds attheblood-brainbarrierandblood-cerebrospinal fluidbarrier:relevancetoneuraldisorders MasanoriTachikawa,Ken-ichiHosoya* Abstract Guanidinocompounds(GCs),suchascreatine,phosphocreatine,guanidinoaceticacid,creatinine,methylguanidine, guanidinosuccinicacid,g-guanidinobutyricacid,b-guanidinopropionicacid,guanidinoethanesulfonicacidanda- guanidinoglutaricacid,arepresentinthemammalianbrain.Althoughcreatineandphosphocreatineplay importantrolesinenergyhomeostasisinthebrain,accumulationofGCsmayinduceepilepticdischargesand convulsions.Thisreviewfocusesonhowphysiologicallyimportantand/orneurotoxicGCsaredistributedinthe brainunderphysiologicalandpathologicalconditions.TransportersforGCsattheblood-brainbarrier(BBB)andthe blood-cerebrospinalfluid(CSF)barrier(BCSFB)haveemergedassubstantialcontributorstoGCsdistributioninthe brain.Creatinetransporter(CRT/solutecarrier(SLC)6A8)expressedattheBBBregulatescreatineconcentrationin thebrain,andrepresentsamajorpathwayforsupplyofcreatinefromthecirculatingbloodtothebrain.CRTmay beakeyfactorfacilitatingblood-to-brainguanidinoacetatetransportinpatientsdeficientinS-adenosylmethionine: guanidinoacetateN-methyltransferase,thecreatinebiosyntheticenzyme,resultingincerebralaccumulationof guanidinoacetate.CRT,taurinetransporter(TauT/SLC6A6)andorganiccationtransporter(OCT3/SLC22A3)expressed attheBCSFBareinvolvedinguanidinoaceticacidorcreatinineeffluxtransportfromCSF.Interestingly,BBBefflux transportofGCs,includingguanidinoacetateandcreatinine,isnegligible,thoughtheBBBhasavarietyofefflux transportsystemsforsyntheticprecursorso

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