Profiling Solute Carrier Transporters in the Human Blood–Brain Barrier

Geier, Ethan G.; Chen, Eugene C.; Webb, Amy; Papp, Audrey C.; Yee, Sook Wah; Sadée, Wolfgang; Giacomini, Kathleen M.

doi:10.1038/clpt.2013.175

Cited by 113 publications

(89 citation statements)

References 5 publications

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“…34 A reduced function OCT2 allele might result in reduced blood-brain barrier transport of smoking cessation pharmacotherapies. 19 The reduced function allele might also result in increased extracellular monoamines in brain in the post-quit period when extracellular monoamine concentrations may be reduced in the context of nicotine withdrawal. 80 Each of these potential effects of a reduced function OCT2 allele in specific organs and tissues might exert effects on smoking cessation pharmacotherapy effectiveness.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 All three genes are expressed in multiple brain regions at lower levels than in the periphery. [19][20][21][22][23] All three proteins serve as low affinity Na + and Cl − independent transport systems for choline, acetylcholine, and monoamines. 24 OCT2 mediates post-synaptic transport of norepinephrine and serotonin 25 and synaptic vesicle transport in cholinergic neurons and neuromuscular junction neurons.…”

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confidence: 99%

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Organic Cation Transporter Variation and Response to Smoking Cessation Therapies

Bergen

Javitz

Krasnow

et al. 2014

Nicotine & Tobacco Research

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Organic Cation Transporter Variation and Response to Smoking Cessation Therapies

Bergen

Javitz

Krasnow

et al. 2014

Nicotine & Tobacco Research

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“…In addition, endothelial cells forming the BBB lack fenestrations in their plasma membranes and have a reduced number of pinocytotic vesicles compared to endothelial cells in other tissues, which restricts transcellular flux (76). Despite this, certain solutes and macromolecules may be transported across the BBB via specific and nonspecific mechanisms, such as passive diffusion and receptor and/or adsorption-mediated transcytosis, or via ATP-binding cassette transporters and solute carrier transporters, which are expressed on cerebral microvessels (75,(77)(78)(79). The transcellular and paracellular routes of entry to the CNS are highly relevant for microbial pathogens.…”

Section: The Blood-brain Barriermentioning

confidence: 99%

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

et al. 2014

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SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

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“…The brain capillary endothelial cells express complex tight junction networks, which, together with metabolising enzymes and drug transporters, constitute the BBB [2]. A number of transporters of the ATP-binding cassette family, including P-glycoprotein (P-gp/Abcb1), breast cancer resistance protein (Bcrp/Abcg2) and multidrug resistance-associated proteins (Mrp's/Abcc's), are localized at the luminal membrane of the endothelial cells [3][4][5][6][7][8][9][10], where they restrict access to the central nervous system for a large number of drug compounds [11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

An Electrically Tight In Vitro Blood–Brain Barrier Model Displays Net Brain-to-Blood Efflux of Substrates for the ABC Transporters, P-gp, Bcrp and Mrp-1

Helms

Hersom

Kuhlmann

et al. 2014

AAPS J

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Abstract. Efflux transporters of the ATP-binding cassette superfamily including breast cancer resistance protein (Bcrp/Abcg2), P-glycoprotein (P-gp/Abcb1) and multidrug resistance-associated proteins (Mrp's/ Abcc's) are expressed in the blood-brain barrier (BBB). The aim of this study was to investigate if a bovine endothelial/rat astrocyte in vitro BBB co-culture model displayed polarized transport of known efflux transporter substrates. The co-culture model displayed low mannitol permeabilities of 0.95±0.1·10 H-etoposide revealed polarized transport favouring the brain-to-blood direction for all substrates. Steady state efflux ratios of 2.5±0.2 for digoxin, 4.4±0.5 for estrone-3-sulphate and 2.4±0.1 for etoposide were observed. These were reduced to 1.1±0.08, 1.4±0.2 and 1.5±0.1, by addition of verapamil (digoxin), Ko143 (estrone-3-sulphate) or zosuquidar+reversan (etoposide), respectively. Brain-toblood permeability of all substrates was investigated in the presence of the efflux transporter inhibitors verapamil, Ko143, zosuquidar, reversan and MK 571 alone or in combinations. Digoxin was mainly transported via P-gp, estrone-3-sulphate via Bcrp and Mrp's and etoposide via P-gp and Mrp's. The expression of P-gp, Bcrp and Mrp-1 was confirmed using immunocytochemistry. The findings indicate that P-gp, Bcrp and at least one isoform of Mrp are functionally expressed in our bovine/rat co-culture model and that the model is suitable for investigations of small molecule transport.KEY WORDS: blood-brain barrier; breast cancer resistance protein; multidrug resistance-associated protein; p-glycoprotein; polarized small molecule transport.

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Profiling Solute Carrier Transporters in the Human Blood–Brain Barrier

Cited by 113 publications

References 5 publications

Organic Cation Transporter Variation and Response to Smoking Cessation Therapies

Organic Cation Transporter Variation and Response to Smoking Cessation Therapies

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

An Electrically Tight In Vitro Blood–Brain Barrier Model Displays Net Brain-to-Blood Efflux of Substrates for the ABC Transporters, P-gp, Bcrp and Mrp-1

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