New Aspects of the Blood-Brain Barrier Transporters; Its Physiological Roles in the Central Nervous System

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概要

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• The blood-brain barrier (BBB) segregates the circulating blood from interstitial fluid in the brain, and restricts drug permeability into the brain. Our latest studies have revealed that the BBB transporters play important physiological roles in maintaining the brain milieu. The BBB supplies creatine to the brain for an energystoring system, and creatine transporter localized at the brain capillary endothelial cells (BCECs) is involved in BBB creatine transport. The BBB is involved in the brain-to-blood efflux transport of the suppressive neurotransmitter, γ-aminobutyric acid, and GAT2/BGT-1 mediates this transport process. BCECs also express serotonin and norepinephrine transporters. Organic anion transporter 3 (OAT3) and ASCT2 are localized at the abluminal membrane of the BCECs. OAT3 is involved in the brain-to-blood efflux of a dopamine metabolite, a uremic toxin and thiopurine nucleobase analogs. ASCT2 plays a role in _L-isomer-selective aspartic acid efflux transport at the BBB. Dehydroepiandrosterone sulfate and small neutral amino acids undergo brain-to-blood efflux transport mediated by organic anion transporting polypeptide 2 and ATA2, respectively. The BBB transporters are regulated by various factors, ATA2 by osmolarity, taurine transporter by TNF-α, and _L-cystine/_L-glutamic acid exchange transporter by oxidative stress. Clarifying the physiological roles of BBB transport systems should give us important information allowing the development of better CNS drugs and improving our understanding of the relationship between CNS disorders and BBB function.

• 公益社団法人日本薬学会の論文
• 2004-10-01

著者

• Ohtsuki Sumio

  Department Of Molecular Biopharmacy And Genetics Graduate School Of Pharmaceutical Sciences Tohoku U

• Ohtsuki Sumio

  Department of Molecular Biopharmacy and Genetics, Graduate School of Pharmaceutical Sciences, Tohoku University : New Industry Creation Hatchery Center, Tohoku University : CREST and SORST of the Japan Science and Technology Agency (JST)

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• Transporter mRNA Expression in a Conditionally Immortalized Rat Small Intestine Epithelial Cell Line (TR-SIE)
• Establishment of Conditionally Immortalized Rat Retinal Pericyte Cell Lines (TR-rPCT) and Their Application in a Co-culture System Using Retinal Capillary Endothelial Cell Line (TR-iBRB2)
• Correlation of Induction of ATP Binding Cassette Transporter A5 (ABCA5) and ABCB1 mRNAs with Differentiation State of Human Colon Tumor(Molecular and Cell Biology)
• mRNA Expression of the ATP-Binding Cassette Transporter Subfamily A (ABCA) in Rat and Human Brain Capillary Endothelial Cells(Biochemistry/Molecular Biology)
• mRNA Expression and Amino Acid Transport Characteristics of Cultured Human Brain Microvascular Endothelial Cells (hBME)
• Functional characterization of the brain-to-blood efflux clearance of human amyloid-β peptide (1-40) across the rat blood-brain barrier
• Localization of norepinephrine and serotonin transporter in mouse brain capillary endothelial cells
• New Aspects of the Blood-Brain Barrier Transporters; Its Physiological Roles in the Central Nervous System

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