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The Role of P-Glycoprotein at the Blood–Brain Barrier in Neurological and Psychiatric Disease

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PET and SPECT in Psychiatry

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Abstract

P-glycoprotein, also known as ABCB1, is an efflux transporter located at endothelial cells of the blood–brain barrier and plays an important role in protecting the brain parenchyma from various neurotoxic substances. These substances are transported across the blood–brain barrier and are called ‘P-gp substrates’. A broad range of P-gp substrates with a great degree of structural diversity exists. In this chapter we discuss the current state of knowledge about this interesting transporter with a special focus on the influence of P-gp on the tissue distribution of pharmaceuticals and drug resistance and the role of changes in P-gp function in psychiatric and neurological disorders.

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Abbreviations

ABC transporters:

ATP-binding cassette transporters

AD:

Alzheimer’s disease

ATP:

Adenosine triphosphate

Aβ:

Amyloid-beta

BBB:

Blood–brain barrier

BCRP:

Breast cancer resistance protein

CBF:

Cerebral blood flow

CNS:

Central nervous system

DDI:

Drug–drug interactions

GIT:

Gastrointestinal tract

JAM:

Junctional adhesion molecules

LRP1:

Low-density lipoprotein receptor-related protein-1

MRI:

Magnetic resonance imaging

MRP:

Multidrug resistance-associated protein

MSD:

Membrane-spanning domain

NBD:

Nucleotide-binding domain

NHP:

Non-human primate

PET:

Positron emission tomography

P-gp:

P-glycoprotein (permeability glycoprotein)

SPECT:

Single photon emission computed tomography

SUV:

Standardized uptake value

TEER:

Transepithelial/endothelial electrical resistance

V T :

Volume of distribution

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Authors and Affiliations

  1. Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Pascalle Mossel & Gert Luurtsema

  2. Department of Neurology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Anna L. Bartels & Peter Paul de Deyn

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  1. Pascalle Mossel
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  2. Anna L. Bartels
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  3. Peter Paul de Deyn
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  4. Gert Luurtsema
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Correspondence to Gert Luurtsema .

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Editors and Affiliations

  1. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Rudi A.J.O. Dierckx

  2. Faculty of Electrical Engineering, Medical Engineering and Computer Science, Offenburg University, Offenburg, Germany

    Andreas Otte

  3. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Erik F. J. de Vries

  4. Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands

    Aren van Waarde

  5. Biomedical Sciences of Cells and Systems, University Medical Center Groningen, Groningen, The Netherlands

    Iris E. Sommer

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Mossel, P., Bartels, A.L., de Deyn, P.P., Luurtsema, G. (2021). The Role of P-Glycoprotein at the Blood–Brain Barrier in Neurological and Psychiatric Disease. In: Dierckx, R.A., Otte, A., de Vries, E.F.J., van Waarde, A., Sommer, I.E. (eds) PET and SPECT in Psychiatry. Springer, Cham. https://doi.org/10.1007/978-3-030-57231-0_3

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