Skip to main content

Advertisement

SpringerLink
Log in

Solute Carriers in the Blood–Brain Barier: Safety in Abundance

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Blood–brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood–brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5, SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the blood–brain barriers has been demonstrated are characterized with a special emphasis put on polarity of transporters localization in a luminal (blood side) versus an abluminal (brain side) membrane.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Notes

  1. Please, note that original nomenclature SLCnXm (for Solute carrier), where n—number of family, X—subfamily, m—individual family member written in italics, was applied for human genome project and now is also used for transporting proteins (SLCnXm).

References

  1. Hartsock A, Nelson WJ (2008) Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778:660–669

    Article  CAS  PubMed  Google Scholar 

  2. Abbott NJ (1001) Permeability and transport of glial blood–brain barriers. Ann N Y Acad Sci 633:378–394

    Article  Google Scholar 

  3. Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC (2013) The blood–brain barrier: an engineering perspective. Front Neuroeng 6:7. doi:10.3389/fnegg.2013.00007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Lewandowsky M (1890) Zur Lehre von der Cerebrospinalflussigkeit. Z Klin Med 40:480–494

    Google Scholar 

  5. Enerson BE, Drewes LR (2006) The rat blood–brain barrier transcriptome. J Cereb Blood Flow Metab 26:959–973

    Article  CAS  PubMed  Google Scholar 

  6. Dahlin A, Royall J, Hohmann JG, Wang J (2009) Expression profiling of the solute carrier gene family in the mouse brain. J Pharmacol Exp Ther 329:558–570

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Geier EG, Chen EC, Webb A, Papp AC, Yee SW, Sadee W, Giacomini KM (2013) Profiling solute carrier transporters in the human blood–brain barrier. Clin Pharmacol Ther 94:636–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C, Suzuki T, Kamiie J, Terasaki T (2011) Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors. J Neurochem 117:333–345

    Article  CAS  PubMed  Google Scholar 

  9. Uchida Y, Tachikawa M, Obuchi W, Hoshi Y, Tomioka Y, Ohtsuki S, Terasaki T (2013) A study protocol for quantitative targeted absolute proteomics (QTAP) by LC-MS/MS: application for inter-strain differences in protein expression levels of transporters, receptors, claudin-5, and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6 J mice. Fluids Barriers CNS 10:21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Roberts LM, Black DS, Raman C, Woodford K, Zhou M, Haggerty JE, Yan AT, Cwirla SE, Grindstaff KK (2008) Subcellular localization of transporters along the rat blood–brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation. Neuroscience 155:423–438

    Article  CAS  PubMed  Google Scholar 

  11. Cornford EM, Hyman S (2005) Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy. NeuroRx 2:27–43

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lee WJ, Hawkins RA, Vina JR, Peterson DR (1998) Glutamine transport by the blood–brain barrier: a possible mechanism for nitrogen removal. Am J Physiol 274:C1101–C1107

    CAS  PubMed  Google Scholar 

  13. O’Kane RL, Hawkins RA (2003) Na+-dependent transport of large neutral amino acids occurs at the abluminal membrane of the blood–brain barrier. Am J Physiol Endocrinol Metab 285:E1167–E1173

    Article  PubMed  Google Scholar 

  14. O’Kane RL, Vina JR, Simpson I, Zaragoza R, Mokashi A, Hawkins RA (2006) Cationic amino acid transport across the blood–brain barrier is mediated exclusively by system y+. Am J Physiol Endocrinol Metab 291:E412–E419

    Article  PubMed  CAS  Google Scholar 

  15. Qosa H, Miller DS, Pasinelli P, Trotti D (2015) Regulation of ABC efflux transporters at blood–brain barrier in health and neurological disorders. Brain Res 1628:298–316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Simpson IA, Carruthers A, Vannucci SJ (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766–1791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Edmond J, Robbins RA, Bergstrom JD, Cole RA, de Vellis J (1987) Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J Neurosci Res 18:551–561

    Article  CAS  PubMed  Google Scholar 

  18. Ebert D, Haller RG, Walton ME (2003) Energy contribution of octanoate to intact rat brain metabolism measured by 13 C nuclear magnetic resonance spectroscopy. J Neurosci 23:5928–5935

    CAS  PubMed  Google Scholar 

  19. Nehlig A, Pereira de Vasconcelos A (1993) Glucose and ketone body utilization by the brain of neonatal rats. Prog Neurobiol 40:163–221

    Article  CAS  PubMed  Google Scholar 

  20. Brown AM (2004) Brain glycogen re-awakened. J Neurochem 89:537–552

    Article  CAS  PubMed  Google Scholar 

  21. Pellerin L, Pellegri G, Bittar PG, Charnay Y, Bouras C, Martin JL, Stella N, Magistretti PJ (1998) Evidence supporting the existence of an activity-dependent astrocyte-neuron lactate shuttle. Dev Neurosci 20:291–299

    Article  CAS  PubMed  Google Scholar 

  22. Pellerin L, Magistretti PJ (2004) Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 10:53–62

    Article  CAS  PubMed  Google Scholar 

  23. Dick AP, Harik SI, Klip A, Walker DM (1984) Identification and characterization of the glucose transporter of the blood–brain barrier by cytochalasin B binding and immunological reactivity. Proc Natl Acad Sci USA 81:7233–7237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Pardridge WM, Boado RJ, Farrell CR (1990) Brain-type glucose transporter (GLUT-1) is selectively localized to the blood–brain barrier. Studies with quantitative western blotting and in situ hybridization. J Biol Chem 265:18035–18040

    CAS  PubMed  Google Scholar 

  25. Boado RJ, Pardridge WM (1994) Measurement of blood–brain barrier GLUT1 glucose transporter and actin mRNA by a quantitative polymerase chain reaction assay. J Neurochem 62:2085–2090

    Article  CAS  PubMed  Google Scholar 

  26. Farrell CL, Pardridge WM (1991) Blood–brain barrier glucose transporter is asymmetrically distributed on brain capillary endothelial lumenal and ablumenal membranes: an electron microscopic immunogold study. Proc Natl Acad Sci USA 88:5779–5783

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Simpson IA, Vannucci SJ, DeJoseph MR, Hawkins RA (2001) Glucose transporter asymmetries in the bovine blood–brain barrier. J Biol Chem 276:12725–12729

    Article  CAS  PubMed  Google Scholar 

  28. Cornford EM, Hyman S, Pardridge WM (1993) An electron microscopic immunogold analysis of developmental up-regulation of the blood–brain barrier GLUT1 glucose transporter. J Cereb Blood Flow Metab 13:841–854

    Article  CAS  PubMed  Google Scholar 

  29. Gerhart DZ, LeVasseur RJ, Broderius MA, Drewes LR (1989) Glucose transporter localization in brain using light and electron immunocytochemistry. J Neurosci Res 22:464–472

    Article  CAS  PubMed  Google Scholar 

  30. Witters LA, Vater CA, Lienhard GE (1985) Phosphorylation of the glucose transporter in vitro and in vivo by protein kinase C. Nature 315:777–778

    Article  CAS  PubMed  Google Scholar 

  31. Devraj K, Klinger ME, Myers RL, Mokashi A, Hawkins RA, Simpson IA (2011) GLUT-1 glucose transporters in the blood–brain barrier: differential phosphorylation. J Neurosci Res 89:1913–1925

    Article  CAS  PubMed  Google Scholar 

  32. Pouliot JF, Beliveau R (1995) Palmitoylation of the glucose transporter in blood–brain barrier capillaries. Biochim Biophys Acta 1234:191–196

    Article  PubMed  Google Scholar 

  33. Maher F, Vannucci SJ, Simpson IA (1993) Glucose transporter isoforms in brain: absence of GLUT3 from the blood–brain barrier. J Cereb Blood Flow Metab 13:342–345

    Article  CAS  PubMed  Google Scholar 

  34. Morgello S, Uson RR, Schwartz EJ, Haber RS (1995) The human blood–brain barrier glucose transporter (GLUT1) is a glucose transporter of gray matter astrocytes. Glia 14:43–54

    Article  CAS  PubMed  Google Scholar 

  35. Regina A, Morchoisne S, Borson ND, McCall AL, Drewes LR, Roux F (2001) Factor(s) released by glucose-deprived astrocytes enhance glucose transporter expression and activity in rat brain endothelial cells. Biochim Biophys Acta 1540:233–242

    Article  CAS  PubMed  Google Scholar 

  36. Meireles M, Martel F, Araujo J, Santos-Buelga C, Gonzalez-Manzano S, Duenas M, de Freitas V, Mateus N, Calhau C, Faria A (2013) Characterization and modulation of glucose uptake in a human blood–brain barrier model. J Membr Biol 246:669–677

    Article  CAS  PubMed  Google Scholar 

  37. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI (1991) Defective glucose transport across the blood–brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med 325:703–709

    Article  PubMed  Google Scholar 

  38. Gordon N, Newton RW (2003) Glucose transporter type1 (GLUT-1) deficiency. Brain Dev 25:477–480

    Article  PubMed  Google Scholar 

  39. Haberlandt E, Karall D, Jud V, Baumgartner SS, Zotter S, Rostasy K, Baumann M, Scholl-Buergi S (2014) Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet. Neuropediatrics 45:117–119

    PubMed  Google Scholar 

  40. Rose RC (1988) Transport of ascorbic acid and other water-soluble vitamins. Biochim Biophys Acta 947:335–366

    Article  CAS  PubMed  Google Scholar 

  41. Burzle M, Hediger MA (2012) Functional and physiological role of vitamin C transporters. Curr Top Membr 70:357–375

    Article  CAS  PubMed  Google Scholar 

  42. Nowis D, Malenda A, Furs K, Oleszczak B, Sadowski R, Chlebowska J, Firczuk M, Bujnicki JM, Staruch AD, Zagozdzon R, Glodkowska-Mrowka E, Szablewski L, Golab J (2014) Statins impair glucose uptake in human cells. BMJ Open Diabetes Res Care 2:e000017

    Article  PubMed  PubMed Central  Google Scholar 

  43. Elfeber K, Kohler A, Lutzenburg M, Osswald C, Galla HJ, Witte OW, Koepsell H (2004) Localization of the Na+-d-glucose cotransporter SGLT1 in the blood–brain barrier. Histochem Cell Biol 121:201–207

    Article  CAS  PubMed  Google Scholar 

  44. Vemula S, Roder KE, Yang T, Bhat GJ, Thekkumkara TJ, Abbruscato TJ (2009) A functional role for sodium-dependent glucose transport across the blood–brain barrier during oxygen glucose deprivation. J Pharmacol Exp Ther 328:487–495

    Article  CAS  PubMed  Google Scholar 

  45. Erokhova L, Horner A, Ollinger N, Siligan C, Pohl P (2016) The sodium glucose cotransporter SGLT1 is an extremely efficient facilitator of passive water transport. J Biol Chem 291:9712–9720

    Article  CAS  PubMed  Google Scholar 

  46. Halestrap AP, Meredith D (2004) The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch 447:619–628

    Article  CAS  PubMed  Google Scholar 

  47. Halestrap AP, Wilson MC (2012) The monocarboxylate transporter family–role and regulation. IUBMB Life 64:109–119

    Article  CAS  PubMed  Google Scholar 

  48. Garcia CK, Goldstein JL, Pathak RK, Anderson RG, Brown MS (1994) Molecular characterization of a membrane transporter for lactate, pyruvate, and other monocarboxylates: implications for the Cori cycle. Cell 76:865–873

    Article  CAS  PubMed  Google Scholar 

  49. Ritzhaupt A, Wood IS, Ellis A, Hosie KB, Shirazi-Beechey SP (1998) Identification and characterization of a monocarboxylate transporter (MCT1) in pig and human colon: its potential to transport l-lactate as well as butyrate. J Physiol 513:719–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gerhart DZ, Enerson BE, Zhdankina OY, Leino RL, Drewes LR (1997) Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats. Am J Physiol 273:E207–E213

    CAS  PubMed  Google Scholar 

  51. Leino RL, Gerhart DZ, Drewes LR (1999) Monocarboxylate transporter (MCT1) abundance in brains of suckling and adult rats: a quantitative electron microscopic immunogold study. Brain Res Dev Brain Res 113:47–54

    Article  CAS  PubMed  Google Scholar 

  52. Broer S, Rahman B, Pellegri G, Pellerin L, Martin JL, Verleysdonk S, Hamprecht B, Magistretti PJ (1997) Comparison of lactate transport in astroglial cells and monocarboxylate transporter 1 (MCT 1) expressing Xenopus laevis oocytes. Expression of two different monocarboxylate transporters in astroglial cells and neurons. J Biol Chem 272:30096–30102

    Article  CAS  PubMed  Google Scholar 

  53. Broer S, Schneider HP, Broer A, Rahman B, Hamprecht B, Deitmer JW (1998) Characterization of the monocarboxylate transporter 1 expressed in Xenopus laevis oocytes by changes in cytosolic pH. Biochem J 333:167–174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Uhernik AL, Tucker C, Smith JP (201) Control of MCT1 function in cerebrovascular endothelial cells by intracellular pH. Brain Res 1376:10–22

  55. Moschen I, Broer A, Galic S, Lang F, Broer S (2012) Significance of short chain fatty acid transport by members of the monocarboxylate transporter family (MCT). Neurochem Res 37:2562–2568

    Article  CAS  PubMed  Google Scholar 

  56. Tsuji A, Saheki A, Tamai I, Terasaki T (1993) Transport mechanism of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors at the blood–brain barrier. J Pharmacol Exp Ther 267:1085–1090

    CAS  PubMed  Google Scholar 

  57. Vijay N, Morris ME (2014) Role of monocarboxylate transporters in drug delivery to the brain. Curr Pharm Des 20:1487–1498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Pardridge WM, Oldendorf WH (1977) Transport of metabolic substrates through the blood–brain barrier. J Neurochem 28:5–12

    Article  CAS  PubMed  Google Scholar 

  59. Smith JP, Drewes LR (2006) Modulation of monocarboxylic acid transporter-1 kinetic function by the cAMP signaling pathway in rat brain endothelial cells. J Biol Chem 281:2053–2060

    Article  CAS  PubMed  Google Scholar 

  60. Liu Z, Sneve M, Haroldson TA, Smith JP, Drewes LR (2016) Regulation of monocarboxylic acid transporter 1 trafficking by the canonical Wnt/beta-catenin pathway in rat brain endothelial cells requires cross-talk with notch signaling. J Biol Chem 291:8059–8069

    Article  CAS  PubMed  Google Scholar 

  61. Soares RV, Do TM, Mabondzo A, Pons G, Chhun S (2016) Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain. Fundam Clin Pharmacol 30:107–116

    Article  CAS  PubMed  Google Scholar 

  62. Kirk P, Wilson MC, Heddle C, Brown MH, Barclay AN, Halestrap AP(2000) CD147 is tightly associated with lactate transporters MCT1 and MCT4 and facilitates their cell surface expression. EMBO J 19:3896–3904

  63. Leino RL, Gerhart DZ, Duelli R, Enerson BE, Drewes LR (2001) Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int 38:519–527

    Article  CAS  PubMed  Google Scholar 

  64. Ito K, Uchida Y, Ohtsuki S, Aizawa S, Kawakami H, Katsukura Y, Kamiie J, Terasaki T (2011) Quantitative membrane protein expression at the blood–brain barrier of adult and younger cynomolgus monkeys. J Pharm Sci 100:3939–3950

    Article  CAS  PubMed  Google Scholar 

  65. Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (2003) Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278:40128–40135

    Article  CAS  PubMed  Google Scholar 

  66. Moog NK, Entringer S, Heim C, Wadhwa PD, Kathmann N, Buss C (2015) Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience. doi:10.1016/j.neuroscience.2015.09.070

    PubMed  Google Scholar 

  67. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM (1992) Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281:21–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Ohtsuki S, Tachikawa M, Takanaga H, Shimizu H, Watanabe M, Hosoya K, Terasaki T (2002) The blood–brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab 22:1327–1335

    Article  CAS  PubMed  Google Scholar 

  69. Broer S, Gether U (2012) The solute carrier 6 family of transporters. Br J Pharmacol 167:256–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Beard E, Braissant O (2010) Synthesis and transport of creatine in the CNS: importance for cerebral functions. J Neurochem 115:297–313

    Article  CAS  PubMed  Google Scholar 

  71. Salomons GS, van Dooren SJ, Verhoeven NM, Marsden D, Schwartz C, Cecil KM, DeGrauw TJ, Jakobs C (2003) X-linked creatine transporter defect: an overview. J Inherit Metab Dis 26:309–318

    Article  CAS  PubMed  Google Scholar 

  72. Mancardi MM, Caruso U, Schiaffino MC, Baglietto MG, Rossi A, Battaglia FM, Salomons GS, Jakobs C, Zara F, Veneselli E, Gaggero R (2007) Severe epilepsy in X-linked creatine transporter defect (CRTR-D). Epilepsia 48:1211–1213

    Article  CAS  PubMed  Google Scholar 

  73. Thurm A, Himelstein D, D’Souza P, Rennert O, Jiang S, Olatunji D, Longo N, Pasquali M, Swedo S, Salomons GS, Carrillo N (2016) Creatine transporter deficiency: screening of males with neurodevelopmental disorders and neurocognitive characterization of a case. J Dev Behav Pediatr 37:322–326

    Article  PubMed  Google Scholar 

  74. Braissant O, Cagnon L, Monnet-Tschudi F, Speer O, Wallimann T, Honegger P, Henry H (2008) Ammonium alters creatine transport and synthesis in a 3D culture of developing brain cells, resulting in secondary cerebral creatine deficiency. Eur J Neurosci 27:1673–1685

    Article  PubMed  Google Scholar 

  75. Braissant O (2010) Ammonia toxicity to the brain: effects on creatine metabolism and transport and protective roles of creatine. Mol Genet Metab 100(Suppl 1):S53–S58

    Article  CAS  PubMed  Google Scholar 

  76. Braissant O (2012) Creatine and guanidinoacetate transport at blood–brain and blood-cerebrospinal fluid barriers. J Inherit Metab Dis 35:655–664

    Article  CAS  PubMed  Google Scholar 

  77. Westergren I, Nystrom B, Hamberger A, Nordborg C, Johansson BB (1994) Concentrations of amino acids in extracellular fluid after opening of the blood–brain barrier by intracarotid infusion of protamine sulfate. J Neurochem 62:159–165

    Article  CAS  PubMed  Google Scholar 

  78. Oldendorf WH (1971) Brain uptake of radiolabeled amino acids, amines, and hexoses after arterial injection. Am J Physiol 221:1629–1639

    CAS  PubMed  Google Scholar 

  79. Boado RJ, Li JY, Nagaya M, Zhang C, Pardridge WM (1999) Selective expression of the large neutral amino acid transporter at the blood–brain barrier. Proc Natl Acad Sci USA 96:12079–12084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fotiadis D, Kanai Y, Palacin M (2013) The SLC3 and SLC7 families of amino acid transporters. Mol Aspects Med 34:139–158

    Article  CAS  PubMed  Google Scholar 

  81. Kageyama T, Nakamura M, Matsuo A, Yamasaki Y, Takakura Y, Hashida M, Kanai Y, Naito M, Tsuruo T, Minato N, Shimohama S (2000) The 4F2hc/LAT1 complex transports l-DOPA across the blood–brain barrier. Brain Res 879:115–121

    Article  CAS  PubMed  Google Scholar 

  82. Dickens D, Webb SD, Antonyuk S, Giannoudis A, Owen A, Radisch S, Hasnain SS, Pirmohamed M (2013) Transport of gabapentin by LAT1 (SLC7A5). Biochem Pharmacol 85:1672–1683

    Article  CAS  PubMed  Google Scholar 

  83. Duelli R, Enerson BE, Gerhart DZ, Drewes LR (2000) Expression of large amino acid transporter LAT1 in rat brain endothelium. J Cereb Blood Flow Metab 20:1557–1562

    Article  CAS  PubMed  Google Scholar 

  84. Boado RJ, Li JY, Tsukamoto H, Pardridge WM (2003) Hypoxia induces de-stabilization of the LAT1 large neutral amino acid transporter mRNA in brain capillary endothelial cells. J Neurochem 85:1037–1042

    Article  CAS  PubMed  Google Scholar 

  85. Sloan JL, Mager S (1999) Cloning and functional expression of a human Na(+) and Cl(−)-dependent neutral and cationic amino acid transporter B(0+). J Biol Chem 274:23740–23745

    Article  CAS  PubMed  Google Scholar 

  86. Berezowski V, Miecz D, Marszalek M, Broer A, Broer S, Cecchelli R, Nalecz KA (2004) Involvement of OCTN2 and B0,+ in the transport of carnitine through an in vitro model of the blood–brain barrier. J Neurochem 91:860–872

    Article  CAS  PubMed  Google Scholar 

  87. Czeredys M, Mysiorek C, Kulikova N, Samluk L, Berezowski V, Cecchelli R, Nalecz K (2008) A polarized localization of amino acid/carnitine transporter B0,+ (ATB0,+) in the blood–brain barrier. Biochem Biophys Res Commun 376:267–270

    Article  CAS  PubMed  Google Scholar 

  88. Michalec K, Mysiorek C, Kuntz M, Berezowski V, Szczepankiewicz AA, Wilczynski GM, Cecchelli R, Nalecz KA (2014) Protein kinase C restricts transport of carnitine by amino acid transporter ATB(0,+) apically localized in the blood–brain barrier. Arch Biochem Biophys 554:28–35

    Article  CAS  PubMed  Google Scholar 

  89. Scafidi S, Fiskum G, Lindauer SL, Bamford P, Shi D, Hopkins I, McKenna MC (2010) Metabolism of acetyl-l-carnitine for energy and neurotransmitter synthesis in the immature rat brain. J Neurochem 114:820–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Nakanishi T, Hatanaka T, Huang W, Prasad PD, Leibach FH, Ganapathy ME, Ganapathy V (2001) Na+- and Cl−-coupled active transport of carnitine by the amino acid transporter ATB(0,+) from mouse colon expressed in HRPE cells and Xenopus oocytes. J Physiol 532:297–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V (2000) Beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem 275:1699–1707

    Article  CAS  PubMed  Google Scholar 

  92. Samluk L, Czeredys M, Skowronek K, Nalecz KA (2012) Protein kinase C regulates amino acid transporter ATB(0+). Biochem Biophys Res Commun 422:64–69

    Article  CAS  PubMed  Google Scholar 

  93. Hatanaka T, Huang W, Nakanishi T, Bridges CC, Smith SB, Prasad PD, Ganapathy ME, Ganapathy V (2002) Transport of d-serine via the amino acid transporter ATB(0,+) expressed in the colon. Biochem Biophys Res Commun 291:291–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Matsui T, Sekiguchi M, Hashimoto A, Tomita U, Nishikawa T, Wada K (1995) Functional comparison of d-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration. J Neurochem 65:454–458

    Article  CAS  PubMed  Google Scholar 

  95. Wolosker H, Blackshaw S, Snyder SH (1999) Serine racemase: a glial enzyme synthesizing d-serine to regulate glutamate-N-methyl-d-aspartate neurotransmission. Proc Natl Acad Sci USA 96:13409–13414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Ennis SR, Kawai N, Ren XD, Abdelkarim GE, Keep RF (1998) Glutamine uptake at the blood–brain barrier is mediated by N-system transport. J Neurochem 71:2565–2573

    Article  CAS  PubMed  Google Scholar 

  97. Xiang J, Ennis SR, Abdelkarim GE, Fujisawa M, Kawai N, Keep RF (2003) Glutamine transport at the blood–brain and blood-cerebrospinal fluid barriers. Neurochem Int 43:279–288

    Article  CAS  PubMed  Google Scholar 

  98. Ruderisch N, Virgintino D, Makrides V, Verrey F (2011) Differential axial localization along the mouse brain vascular tree of luminal sodium-dependent glutamine transporters Snat1 and Snat3. J Cereb Blood Flow Metab 31:1637–1647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Boulland JL, Rafiki A, Levy LM, Storm-Mathisen J, Chaudhry FA (2003) Highly differential expression of SN1, a bidirectional glutamine transporter, in astroglia and endothelium in the developing rat brain. Glia 41:260–275

    Article  PubMed  Google Scholar 

  100. Dolgodilina E, Imobersteg S, Laczko E, Welt T, Verrey F, Makrides V (2015) Brain interstitial fluid glutamine homeostasis is controlled by blood–brain barrier SLC7A5/LAT1 amino acid transporter. J Cereb Blood Flow Metab. doi:10.1177/0271678X15609331

    PubMed  Google Scholar 

  101. Stoll J, Wadhwani KC, Smith QR (1993) Identification of the cationic amino acid transporter (System y+) of the rat blood–brain barrier. J Neurochem 60:1956–1959

    Article  CAS  PubMed  Google Scholar 

  102. Skowronska M, Zielinska M, Wojcik-Stanaszek L, Ruszkiewicz J, Milatovic D, Aschner M, Albrecht J (2012) Ammonia increases paracellular permeability of rat brain endothelial cells by a mechanism encompassing oxidative/nitrosative stress and activation of matrix metalloproteinases. J Neurochem 121:125–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Zielinska M, Popek M, Albrecht J (2014) Roles of changes in active glutamine transport in brain edema development during hepatic encephalopathy: an emerging concept. Neurochem Res 39:599–604

    Article  CAS  PubMed  Google Scholar 

  104. Hosoya K, Sugawara M, Asaba H, Terasaki T (1999) Blood–brain barrier produces significant efflux of L-aspartic acid but not d-aspartic acid: in vivo evidence using the brain efflux index method. J Neurochem 73:1206–1211

    Article  CAS  PubMed  Google Scholar 

  105. Jensen AA, Fahlke C, Bjorn-Yoshimoto WE, Bunch L (2015) Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities. Curr Opin Pharmacol 20:116–123

    Article  CAS  PubMed  Google Scholar 

  106. O’Kane RL, Martinez-Lopez I, DeJoseph MR, Vina JR, Hawkins RA (1999) Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood–brain barrier. A mechanism for glutamate removal. J Biol Chem 274:31891–31895

    Article  PubMed  Google Scholar 

  107. Cederberg HH, Uhd NC, Brodin B (2014) Glutamate efflux at the blood–brain barrier: cellular mechanisms and potential clinical relevance. Arch Med Res 45:639–645

    Article  CAS  PubMed  Google Scholar 

  108. Helms HC, Madelung R, Waagepetersen HS, Nielsen CU, Brodin B (2012) In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate. Glia 60:882–893

    Article  PubMed  Google Scholar 

  109. Hosoya K, Tomi M, Ohtsuki S, Takanaga H, Saeki S, Kanai Y, Endou H, Naito M, Tsuruo T, Terasaki T (2002) Enhancement of L-cystine transport activity and its relation to xCT gene induction at the blood–brain barrier by diethyl maleate treatment. J Pharmacol Exp Ther 302:225–231

    Article  CAS  PubMed  Google Scholar 

  110. Brigham MP, Stein WH, Moore S (1960) The concentrations of cysteine and cystine in human blood plasma. J Clin Invest 39:1633–1638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Karelson E, Bogdanovic N, Garlind A, Winblad B, Zilmer K, Kullisaar T, Vihalemm T, Kairane C, Zilmer M (2001) The cerebrocortical areas in normal brain aging and in Alzheimer’s disease: noticeable differences in the lipid peroxidation level and in antioxidant defense. Neurochem Res 26:353–361

    Article  CAS  PubMed  Google Scholar 

  112. Tetsuka K, Takanaga H, Ohtsuki S, Hosoya K, Terasaki T (2003) The l-isomer-selective transport of aspartic acid is mediated by ASCT2 at the blood–brain barrier. J Neurochem 87:891–901

    Article  CAS  PubMed  Google Scholar 

  113. Tayarani I, Lefauconnier JM, Roux F, Bourre JM (1987) Evidence for an alanine, serine, and cysteine system of transport in isolated brain capillaries. J Cereb Blood Flow Metab 7:585–591

    Article  CAS  PubMed  Google Scholar 

  114. Sakai K, Shimizu H, Koike T, Furuya S, Watanabe M (2003) Neutral amino acid transporter ASCT1 is preferentially expressed in l-ser-synthetic/storing glial cells in the mouse brain with transient expression in developing capillaries. J Neurosci 23:550–560

    CAS  PubMed  Google Scholar 

  115. Sanchez del Pino MM, Hawkins RA, Peterson DR (1992) Neutral amino acid transport by the blood–brain barrier. Membrane vesicle studies. J Biol Chem 267:25951–25957

    CAS  PubMed  Google Scholar 

  116. Takanaga H, Tokuda N, Ohtsuki S, Hosoya K, Terasaki T (2002) ATA2 is predominantly expressed as system A at the blood–brain barrier and acts as brain-to-blood efflux transport for l-proline. Mol Pharmacol 61:1289–1296

    Article  CAS  PubMed  Google Scholar 

  117. Alfieri RR, Petronini PG, Bonelli MA, Caccamo AE, Cavazzoni A, Borghetti AF, Wheeler KP (2001) Osmotic regulation of ATA2 mRNA expression and amino acid transport System A activity. Biochem Biophys Res Commun 283:174–178

    Article  CAS  PubMed  Google Scholar 

  118. O’Kane RL, Vina JR, Simpson I, Hawkins RA (2004) Na+ -dependent neutral amino acid transporters A, ASC, and N of the blood–brain barrier: mechanisms for neutral amino acid removal. Am J Physiol Endocrinol Metab 287:E622–E629

    Article  PubMed  Google Scholar 

  119. Sanchez del Pino MM, Peterson DR, Hawkins RA (1995) Neutral amino acid transport characterization of isolated luminal and abluminal membranes of the blood–brain barrier. J Biol Chem 270:14913–14918

    Article  CAS  PubMed  Google Scholar 

  120. Takanaga H, Mackenzie B, Peng JB, Hediger MA (2005) Characterization of a branched-chain amino-acid transporter SBAT1 (SLC6A15) that is expressed in human brain. Biochem Biophys Res Commun 337:892–900

    Article  CAS  PubMed  Google Scholar 

  121. Anderson CM, Ganapathy V, Thwaites DT (2008) Human solute carrier SLC6A14 is the beta-alanine carrier. J Physiol 586:4061–4067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Kang YS, Ohtsuki S, Takanaga H, Tomi M, Hosoya K, Terasaki T (2002) Regulation of taurine transport at the blood–brain barrier by tumor necrosis factor-alpha, taurine and hypertonicity. J Neurochem 83:1188–1195

    Article  CAS  PubMed  Google Scholar 

  123. Albrecht J, Schousboe A (2005) Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res 30:1615–1621

    Article  CAS  PubMed  Google Scholar 

  124. Hilgier W, Oja SS, Saransaari P, Albrecht J (2005) Taurine prevents ammonia-induced accumulation of cyclic GMP in rat striatum by interaction with GABAA and glycine receptors. Brain Res 1043:242–246

    Article  CAS  PubMed  Google Scholar 

  125. Hilgier W, Olson JE, Albrecht J (1996) Relation of taurine transport and brain edema in rats with simple hyperammonemia or liver failure. J Neurosci Res 45:69–74

    Article  CAS  PubMed  Google Scholar 

  126. Faff L, Reichenbach A, Albrecht J (1997) Two modes of stimulation by ammonia of taurine release from cultured rabbit Muller cells. Neurochem Int 31:301–305

    Article  CAS  PubMed  Google Scholar 

  127. Zielinska M, Zablocka B, Albrecht J (2003) Effect of ammonia on taurine transport in C6 glioma cells. Adv Exp Med Biol 526:463–470

    Article  CAS  PubMed  Google Scholar 

  128. Lee NY, Kang YS (2004) The brain-to-blood efflux transport of taurine and changes in the blood–brain barrier transport system by tumor necrosis factor-alpha. Brain Res 1023:141–147

    Article  CAS  PubMed  Google Scholar 

  129. Rasgado-Flores H, Mokashi A, Hawkins RA (2012) Na(+)-dependent transport of taurine is found only on the abluminal membrane of the blood–brain barrier. Exp Neurol 233:457–462

    Article  CAS  PubMed  Google Scholar 

  130. Broer S, Brookes N (2001) Transfer of glutamine between astrocytes and neurons. J Neurochem 77:705–719

    Article  CAS  PubMed  Google Scholar 

  131. Skowronska M, Albrecht J (2012) Alterations of blood brain barrier function in hyperammonemia: an overview. Neurotox Res 21:236–244

    Article  CAS  PubMed  Google Scholar 

  132. Kakee A, Takanaga H, Terasaki T, Naito M, Tsuruo T, Sugiyama Y (2001) Efflux of a suppressive neurotransmitter, GABA, across the blood–brain barrier. J Neurochem 79:110–118

    Article  CAS  PubMed  Google Scholar 

  133. Liu QR, Lopez-Corcuera B, Mandiyan S, Nelson H, Nelson N (1993) Molecular characterization of four pharmacologically distinct gamma-aminobutyric acid transporters in mouse brain. J Biol Chem 268:2106–2112

    CAS  PubMed  Google Scholar 

  134. Takanaga H, Ohtsuki S, Hosoya K, Terasaki T (2001) GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood–brain barrier. J Cereb Blood Flow Metab 21:1232–1239

    Article  CAS  PubMed  Google Scholar 

  135. Al-Sarraf H (2002) Transport of 14 C-gamma-aminobutyric acid into brain, cerebrospinal fluid and choroid plexus in neonatal and adult rats. Brain Res Dev Brain Res 139:121–129

    Article  CAS  PubMed  Google Scholar 

  136. Wakayama K, Ohtsuki S, Takanaga H, Hosoya K, Terasaki T (2002) Localization of norepinephrine and serotonin transporter in mouse brain capillary endothelial cells. Neurosci Res 44:173–180

    Article  CAS  PubMed  Google Scholar 

  137. Young LW, Darios ES, Watts SW (2015) An immunohistochemical analysis of SERT in the blood–brain barrier of the male rat brain. Histochem Cell Biol 144:321–329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Allen DD, Smith QR (2001) Characterization of the blood–brain barrier choline transporter using the in situ rat brain perfusion technique. J Neurochem 76:1032–1041

    Article  CAS  PubMed  Google Scholar 

  139. Okuda T, Haga T, Kanai Y, Endou H, Ishihara T, Katsura I (2000) Identification and characterization of the high-affinity choline transporter. Nat Neurosci 3:120–125

    Article  CAS  PubMed  Google Scholar 

  140. Friedrich A, George RL, Bridges CC, Prasad PD, Ganapathy V (2001) Transport of choline and its relationship to the expression of the organic cation transporters in a rat brain microvessel endothelial cell line (RBE4). Biochim Biophys Acta 1512:299–307

    Article  CAS  PubMed  Google Scholar 

  141. Iwao B, Yara M, Hara N, Kawai Y, Yamanaka T, Nishihara H, Inoue T, Inazu M (2016) Functional expression of choline transporter like-protein 1 (CTL1) and CTL2 in human brain microvascular endothelial cells. Neurochem Int 93:40–50

    Article  CAS  PubMed  Google Scholar 

  142. Pacholczyk T, Blakely RD, Amara SG (1991) Expression cloning of a cocaine- and antidepressant-sensitive human noradrenaline transporter. Nature 350:350–354

    Article  CAS  PubMed  Google Scholar 

  143. Lincoln J (1995) Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline. Pharmacol Ther 68:473–501

    Article  CAS  PubMed  Google Scholar 

  144. Lasbennes F, Sercombe R, Seylaz J (1983) Monoamine oxidase activity in brain microvessels determined using natural and artificial substrates: relevance to the blood–brain barrier. J Cereb Blood Flow Metab 3:521–528

    Article  CAS  PubMed  Google Scholar 

  145. Hosoya K, Tachikawa M (2011) Roles of organic anion/cation transporters at the blood–brain and blood-cerebrospinal fluid barriers involving uremic toxins. Clin Exp Nephrol 15:478–485

    Article  CAS  PubMed  Google Scholar 

  146. Ohtsuki S, Asaba H, Takanaga H, Deguchi T, Hosoya K, Otagiri M, Terasaki T (2002) Role of blood–brain barrier organic anion transporter 3 (OAT3) in the efflux of indoxyl sulfate, a uremic toxin: its involvement in neurotransmitter metabolite clearance from the brain. J Neurochem 83:57–66

    Article  CAS  PubMed  Google Scholar 

  147. Mori S, Takanaga H, Ohtsuki S, Deguchi T, Kang YS, Hosoya K, Terasaki T (2003) Rat organic anion transporter 3 (rOAT3) is responsible for brain-to-blood efflux of homovanillic acid at the abluminal membrane of brain capillary endothelial cells. J Cereb Blood Flow Metab 23:432–440

    Article  CAS  PubMed  Google Scholar 

  148. Sweet DH, Chan LM, Walden R, Yang XP, Miller DS, Pritchard JB (2003) Organic anion transporter 3 (Slc22a8) is a dicarboxylate exchanger indirectly coupled to the Na+ gradient. Am J Physiol Renal Physiol 284:F763–F769

    Article  CAS  PubMed  Google Scholar 

  149. Kikuchi R, Kusuhara H, Sugiyama D, Sugiyama Y (2003) Contribution of organic anion transporter 3 (Slc22a8) to the elimination of p-aminohippuric acid and benzylpenicillin across the blood–brain barrier. J Pharmacol Exp Ther 306:51–58

    Article  CAS  PubMed  Google Scholar 

  150. Kikuchi T, Okamura T, Wakizaka H, Okada M, Odaka K, Yui J, Tsuji AB, Fukumura T, Zhang MR (2014) OAT3-mediated extrusion of the 99mTc-ECD metabolite in the mouse brain. J Cereb Blood Flow Metab 34:585–588

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Asaba H, Hosoya K, Takanaga H, Ohtsuki S, Tamura E, Takizawa T, Terasaki T (2000) Blood–brain barrier is involved in the efflux transport of a neuroactive steroid, dehydroepiandrosterone sulfate, via organic anion transporting polypeptide 2. J Neurochem 75:1907–1916

    Article  CAS  PubMed  Google Scholar 

  152. Gao B, Stieger B, Noe B, Fritschy JM, Meier PJ (1999) Localization of the organic anion transporting polypeptide 2 (Oatp2) in capillary endothelium and choroid plexus epithelium of rat brain. J Histochem Cytochem 47:1255–1264

    Article  CAS  PubMed  Google Scholar 

  153. Sugiyama D, Kusuhara H, Shitara Y, Abe T, Meier PJ, Sekine T, Endou H, Suzuki H, Sugiyama Y (2001) Characterization of the efflux transport of 17beta-estradiol-D-17beta-glucuronide from the brain across the blood–brain barrier. J Pharmacol Exp Ther 298:316–322

    CAS  PubMed  Google Scholar 

  154. Gao B, Hagenbuch B, Kullak-Ublick GA, Benke D, Aguzzi A, Meier PJ (2000) Organic anion-transporting polypeptides mediate transport of opioid peptides across blood–brain barrier. J Pharmacol Exp Ther 294:73–79

    CAS  PubMed  Google Scholar 

  155. Guo Y, Jiang L (2016) Organic anion transporting polypeptide 2 transports valproic acid in rat brain microvascular endothelial cells. Neurol Res 38:634–639

    Article  CAS  PubMed  Google Scholar 

  156. Sugiyama D, Kusuhara H, Taniguchi H, Ishikawa S, Nozaki Y, Aburatani H, Sugiyama Y (2003) Functional characterization of rat brain-specific organic anion transporter (Oatp14) at the blood–brain barrier: high affinity transporter for thyroxine. J Biol Chem 278:43489–43495

    Article  CAS  PubMed  Google Scholar 

  157. Mayerl S, Muller J, Bauer R, Richert S, Kassmann CM, Darras VM, Buder K, Boelen A, Visser TJ, Heuer H (2014) Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. J Clin Invest 124:1987–1999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Lin CJ, Tai Y, Huang MT, Tsai YF, Hsu HJ, Tzen KY, Liou HH (2010) Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood–brain barrier and MPTP-induced dopaminergic toxicity in rodents. J Neurochem 114:717–727

    Article  CAS  PubMed  Google Scholar 

  159. Wu KC, Lu YH, Peng YH, Tsai TF, Kao YH, Yang HT, Lin CJ (2015) Decreased expression of organic cation transporters, Oct1 and Oct2, in brain microvessels and its implication to MPTP-induced dopaminergic toxicity in aged mice. J Cereb Blood Flow Metab 35:37–47

    Article  CAS  PubMed  Google Scholar 

  160. Busch AE, Quester S, Ulzheimer JC, Waldegger S, Gorboulev V, Arndt P, Lang F, Koepsell H (1996) Electrogenic properties and substrate specificity of the polyspecific rat cation transporter rOCT1. J Biol Chem 271:32599–32604

    Article  CAS  PubMed  Google Scholar 

  161. Kido Y, Tamai I, Ohnari A, Sai Y, Kagami T, Nezu J, Nikaido H, Hashimoto N, Asano M, Tsuji A (2001) Functional relevance of carnitine transporter OCTN2 to brain distribution of l-carnitine and acetyl-l-carnitine across the blood–brain barrier. J Neurochem 79:959–969

    Article  CAS  PubMed  Google Scholar 

  162. Miecz D, Januszewicz E, Czeredys M, Hinton BT, Berezowski V, Cecchelli R, Nalecz KA (2008) Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood–brain barrier. J Neurochem 104:113–123

    CAS  PubMed  Google Scholar 

  163. Friedrich A, Prasad PD, Freyer D, Ganapathy V, Brust P (2003) Molecular cloning and functional characterization of the OCTN2 transporter at the RBE4 cells, an in vitro model of the blood–brain barrier. Brain Res 968:69–79

    Article  CAS  PubMed  Google Scholar 

  164. Okura T, Kato S, Deguchi Y (2014) Functional expression of organic cation/carnitine transporter 2 (OCTN2/SLC22A5) in human brain capillary endothelial cell line hCMEC/D3, a human blood–brain barrier model. Drug Metab Pharmacokinet 29:69–74

    Article  CAS  PubMed  Google Scholar 

  165. Wu X, Prasad PD, Leibach FH, Ganapathy V (1998) cDNA sequence, transport function, and genomic organization of human OCTN2, a new member of the organic cation transporter family. Biochem Biophys Res Commun 246:589–595

    Article  CAS  PubMed  Google Scholar 

  166. Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, Tsuji A (1998) Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 273:20378–20382

    Article  CAS  PubMed  Google Scholar 

  167. Czeredys M, Samluk L, Michalec K, Tulodziecka K, Skowronek K, Nalecz KA (2013) Caveolin-1–a novel interacting partner of organic cation/carnitine transporter (Octn2): effect of protein kinase C on this interaction in rat astrocytes. PLoS One 8:e82105

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  168. Shinawi M, Gruener N, Lerner A (1998) CSF levels of carnitine in children with meningitis, neurologic disorders, acute gastroenteritis, and seizure. Neurology 50:1869–1871

    Article  CAS  PubMed  Google Scholar 

  169. Bennett KM, Liu J, Hoelting C, Stoll J (2011) Expression and analysis of two novel rat organic cation transporter homologs, SLC22A17 and SLC22A23. Mol Cell Biochem 352:143–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Miyamoto T, Asaka R, Suzuki A, Takatsu A, Kashima H, Shiozawa T (2011) Immunohistochemical detection of a specific receptor for lipocalin2 (solute carrier family 22 member 17, SLC22A17) and its prognostic significance in endometrial carcinoma. Exp Mol Pathol 91:563–568

    Article  CAS  PubMed  Google Scholar 

  171. Serrano Leon A, Amir Shaghaghi M, Yurkova N, Bernstein CN, El-Gabalawy H, Eck P (2014) Single-nucleotide polymorphisms in SLC22A23 are associated with ulcerative colitis in a Canadian white cohort. Am J Clin Nutr 100:289–294

    Article  PubMed  CAS  Google Scholar 

  172. Okura T, Higuchi K, Kitamura A, Deguchi Y (2014) Proton-coupled organic cation antiporter-mediated uptake of apomorphine enantiomers in human brain capillary endothelial cell line hCMEC/D3. Biol Pharm Bull 37:286–291

    Article  CAS  PubMed  Google Scholar 

  173. Mehta DC, Short JL, Nicolazzo JA (2013) Memantine transport across the mouse blood–brain barrier is mediated by a cationic influx H+ antiporter. Mol Pharm 10:4491–4498

    Article  CAS  PubMed  Google Scholar 

  174. Carvey PM, Hendey B, Monahan AJ (2009) The blood–brain barrier in neurodegenerative disease: a rhetorical perspective. J Neurochem 111:291–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Prasad S, Sajja RK, Naik P, Cucullo L (2014) Diabetes mellitus and blood–brain barrier dysfunction: an overview. J Pharmacovigil 2:125

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Part of this manuscript quotes the results obtained by my team during realization of Grants 4427/B/P01/2010/38 and 2012/07/B/NZ3/00225 financed by the National Science Centre in Poland.

Author information

Authors and Affiliations

  1. Laboratory of Transport through Biomembranes, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 3 Pasteur Str., 02-093, Warsaw, Poland

    Katarzyna A. Nałęcz

Authors
  1. Katarzyna A. Nałęcz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Katarzyna A. Nałęcz.

Ethics declarations

Conflict of Interest

The author declares no conflict of interest.

Additional information

This work is dedicated to Prof. Jan Albrecht with acknowledgements for his contribution to science and scientific society.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nałęcz, K.A. Solute Carriers in the Blood–Brain Barier: Safety in Abundance. Neurochem Res 42, 795–809 (2017). https://doi.org/10.1007/s11064-016-2030-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-016-2030-x

Keywords

Search

Navigation