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Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

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Abstract

The human placenta fulfills a variety of essential functions during prenatal life. Several ABC transporters are expressed in the human placenta, where they play a role in the transport of endogenous compounds and may protect the fetus from exogenous compounds such as therapeutic agents, drugs of abuse, and other xenobiotics. To date, considerable progress has been made toward understanding ABC transporters in the placenta. Recent studies on the expression and functional activities are discussed. This review discusses the placental expression and functional roles of several members of ABC transporter subfamilies B, C, and G including MDR1/P-glycoprotein, the MRPs, and BCRP, respectively. Since placental ABC transporters modulate fetal exposure to various compounds, an understanding of their functional and regulatory mechanisms will lead to more optimal medication use when necessary in pregnancy.

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Abbreviations

ABC:

ATP binding cassette

APS:

Antiphospholipid syndrome

BBB:

Blood–brain barrier

BCRP:

Breast cancer resistance protein

BPA:

Bisphenol A

BSEP:

Bile salt export pump

CAR:

Constitutive androstane receptor

DNP-SG:

2,4-dinitrophenyl-S-glutathione

EP:

E-prostanoid

ER:

Estrogen receptor

FDA:

Food and Drug Administration

GSSG:

Glutathione disulfide

HDL-C:

High density lipoprotein cholesterol

ICP:

Intrahepatic cholestasis of pregnancy

IL:

Interleukin

IV:

Intravenous

LDL:

Low density lipoprotein

LOX-1:

Oxidized LDL receptor-1

LPS:

Lipopolysaccharides

LXR:

Liver X receptor

MDCK:

Madin-Darby canine kidney

MDR:

Multidrug resistance protein

MRP:

Multidrug resistance associated proteins

MTX:

Methotrexate

NBD:

Nucleotide binding domain

NTCP:

Na+-taurocholate cotransporting polypeptide

OATP:

Organic anion transporting polypeptides

Ox-LDL:

Oxidized low density lipoprotein

PCR:

Polymerase chain reaction

PET:

Positron emission tomography

PGE2:

Prostaglandin E2

P-gp:

P-glycoprotein

PhIP:

2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine

poly(I:C):

Polyinosinic/Polycytidylic

PPARγ:

Peroxisome proliferator-activator receptor γ

PR:

Progesterone receptor

PXR:

Pregnane X receptor

SGA:

Small for gestational age

TMD:

Transmembrane domains

TNF:

Tumor necrosis factor-α

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ACKNOWLEDGMENTS AND DISCLOSURES

The authors gratefully acknowledge the following sources of support: The Thomas F. and Kate Miller Jeffress Memorial Trust, the VCU School of Pharmacy, the National Institutes of Health (MD002254), VCU Presidential Research Incentive Program and grant P01DA032507 from the National Institute on Drug Abuse.

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Author notes

  1. Soniya S. Vaidya

    Present address: Novartis Institutes of Biomedical Research, Cambridge, Massachusetts, USA

  2. Andrei M. Mikheev

    Present address: Department of Neurosurgery, Institute of Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington, 98109, USA

  3. Kelly E. Desino

    Present address: Abbvie Inc, North Chicago, Illinois, USA

Authors and Affiliations

  1. Department of Pharmaceutics, Virginia Commonwealth University School of Pharmacy, Richmond, Virginia, 23298-0533, USA

    Anand A. Joshi, Soniya S. Vaidya, Abner N. Nyandege & Phillip M. Gerk

  2. Department of Clinical Pharmacology and Toxicology, University of Zurich Hospital, Zurich, Switzerland

    Marie V. St-Pierre

  3. Department of Pharmaceutics, University of Washington School of Pharmacy, Seattle, Washington, USA

    Andrei M. Mikheev & Jashvant D. Unadkat

  4. Department of Pharmaceutical Chemistry, University of Kansas School of Pharmacy, Lawrence, Kansas, USA

    Kelly E. Desino & Kenneth L. Audus

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  1. Anand A. Joshi
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Correspondence to Phillip M. Gerk.

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Joshi, A.A., Vaidya, S.S., St-Pierre, M.V. et al. Placental ABC Transporters: Biological Impact and Pharmaceutical Significance. Pharm Res 33, 2847–2878 (2016). https://doi.org/10.1007/s11095-016-2028-8

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  • DOI: https://doi.org/10.1007/s11095-016-2028-8

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