Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
Regular Articles
Effect of Tacrolimus on Activity and Expression of P-Glycoprotein and ATP-Binding Cassette Transporter A5 (ABCA5) Proteins in Hematoencephalic Barrier Cells
Claudia Andrea Quezada, Wallys Ximena Garrido, Mauricio Alejandro González-Oyarzún, María Cecilia Rauch, Mónica Roxana Salas, Rody Enrique San Martín, Alejandro Andrés Claude, Alejandro Javier Yañez, Juan Carlos Slebe, Juan Guillermo Cárcamo
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Keywords: multidrug resistance, tacrolimus, blood-brain barrier, multidrug resistance protein 1, ATP-binding cassette transporter A5, ATP-binding cassette protein
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2008 Volume 31 Issue 10 Pages 1911-1916

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Abstract

Tacrolimus is an agent used in clinical immunosuppressive drug therapies. A wide spectrum of adverse effects has been reported in association with this immunosuppressor, including neurotoxic effect. The upper limit of therapeutic blood concentrations of tacrolimus has been described as 30 ng/ml in immunosuppressed patients. We investigated the effect of this therapeutic dose of tacrolimus on the expression and activity of the multidrug resistance protein 1 (MDR1 or Pgp, P-glycoprotein) and ATP-binding cassette transporters A5 (ABCA5) in human brain microvascular endothelial cells (HBMEC), derived from Blood-Brain Barrier (BBB) endothelium, these being the most predominantly expressed transcripts in these cells. The expression and activity of MDR1 transporter decreased with 30 ng/ml tacrolimus. The cell viability was not changed with the therapeutic dose used. By contrast, ABCA5 transcripts, of unknown role as yet, increased their expression at this concentration. We propose that the secondary cytotoxic effects of this immunosuppressor on CSN, besides the functional blockade related to multidrug resistance proteins, such as MDR1, and probably ABCA5, could be linked to variations in the expression levels of these proteins at the BBB.

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© 2008 The Pharmaceutical Society of Japan
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