Role of Two Efflux Proteins, ABCB1 and ABCG2 in Blood-Brain Barrier Transport of Bromocriptine in a Murine Model of MPTP-Induced Dopaminergic Degeneration

Authors

  • Sarah Vautier University Paris Sud XI
  • Aline Milane University Paris Sud XI
  • Christine Fernandez University Paris Sud XI
  • Helene Chacun University Paris Sud XI
  • Lucette Lacomblez Pitie-Salpetriere Hospital
  • Robert Farinotti University Paris Sud XI

DOI:

https://doi.org/10.18433/J3B596

Abstract

Purpose: MPTP-induced dopaminergic degeneration is an experimental model commonly used to explore Parkinson’s disease. Cerebral drug transport by ABC transporters in MPTP models has never been reported. Methods: We have investigated the transport of bromocriptine through the blood-brain barrier (BBB) in a MPTP model to understand the influence of the dopaminergic degeneration on ABCB1 and ABCG2. Results: We have shown that in MPTP treated mice, bromocriptine is widely distributed to brain (2.3-fold versus control, p<0.001) suggesting either disruption of BBB or alteration of active efflux of the drug. The investigation of BBB did not evidence a modification of permeability. Studies of ABCB1 and ABCG2 activity showed that MPTP intoxication did not alter their functionality. Conversely, ABCG2 expression studied on brain capillaries from MPTP-treated mice was decreased (1.3-fold, p<0.05) and ABCB1 expression increased (1.43-fold, p<0.05) as an off-setting of brain transport. Conclusions: These data demonstrate that MPTP intoxication does not alter BBB permeability. However, bromocriptine brain distribution is increased in MPTP animals. Hence, MPTP may interact with another transport mechanism such as uptake and/or other efflux transporters. Inflammation and Parkinson’s-like lesions induced by MPTP intoxication could lead to modification of drug pharmacokinetics and have clinical consequences, such as neurotoxicity.

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Author Biographies

Sarah Vautier, University Paris Sud XI

University Paris Sud XI Department of Clinical Pharmacy EA2706 Chatenay-Malabry France

Aline Milane, University Paris Sud XI

University Paris Sud XI Department of Clinical Pharmacy EA2706 Chatenay-Malabry France

Christine Fernandez, University Paris Sud XI

University Paris Sud XI Department of Clinical Pharmacy EA2706 Chatenay-Malabry France

Helene Chacun, University Paris Sud XI

University Paris Sud XI Department of Galenic Pharmacy Chatenay-Malabry France

Lucette Lacomblez, Pitie-Salpetriere Hospital

Neurology Unit Pitie-Salpetriere Hospital Assistance Publique-Hopitaux de Paris France

Robert Farinotti, University Paris Sud XI

University Paris Sud XI Department of Clinical Pharmacy EA2706 Chatenay-Malabry France

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Published

2009-08-09

How to Cite

Vautier, S., Milane, A., Fernandez, C., Chacun, H., Lacomblez, L., & Farinotti, R. (2009). Role of Two Efflux Proteins, ABCB1 and ABCG2 in Blood-Brain Barrier Transport of Bromocriptine in a Murine Model of MPTP-Induced Dopaminergic Degeneration. Journal of Pharmacy & Pharmaceutical Sciences, 12(2), 199–208. https://doi.org/10.18433/J3B596

Issue

Section

Pharmaceutical Sciences; Review Articles