Pharmaceutical Research

, Volume 33, Issue 12, pp 2847–2878 | Cite as

Placental ABC Transporters: Biological Impact and Pharmaceutical Significance

  • Anand A. Joshi
  • Soniya S. Vaidya
  • Marie V. St-Pierre
  • Andrei M. Mikheev
  • Kelly E. Desino
  • Abner N. Nyandege
  • Kenneth L. Audus
  • Jashvant D. Unadkat
  • Phillip M. Gerk
Expert Review

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.

KEY WORDS

breast cancer resistance protein drug transport multidrug resistance-associated protein P-glycoprotein placenta regulation of expression 

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

Notes

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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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Anand A. Joshi
    • 1
  • Soniya S. Vaidya
    • 1
    • 2
  • Marie V. St-Pierre
    • 3
  • Andrei M. Mikheev
    • 4
    • 5
  • Kelly E. Desino
    • 6
    • 7
  • Abner N. Nyandege
    • 1
  • Kenneth L. Audus
    • 6
  • Jashvant D. Unadkat
    • 4
  • Phillip M. Gerk
    • 1
  1. 1.Department of PharmaceuticsVirginia Commonwealth University School of PharmacyRichmondUSA
  2. 2.Novartis Institutes of Biomedical ResearchCambridgeUSA
  3. 3.Department of Clinical Pharmacology and ToxicologyUniversity of Zurich HospitalZurichSwitzerland
  4. 4.Department of PharmaceuticsUniversity of Washington School of PharmacySeattleUSA
  5. 5.Department of Neurosurgery, Institute of Stem Cell and Regenerative MedicineUniversity of Washington School of MedicineSeattleUSA
  6. 6.Department of Pharmaceutical ChemistryUniversity of Kansas School of PharmacyLawrenceUSA
  7. 7.Abbvie IncNorth ChicagoUSA

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