Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells

Quezada, CA; Garrido, WX; Gonzalez-Oyarzun, MA; Rauch MC; Salas, MR; Martin, RES; Claude, AA; Yanez, AJ; Slebe, JC; Carcamo, JG

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. © 2008 Pharmaceutical Society of Japan.

Más información

Título según WOS: Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells
Título según SCOPUS: Effect of tacrolimus on activity and expression of P-glycoprotein and ATP-binding cassette transporter A5 (ABCA5) proteins in hematoencephalic barrier cells
Título de la Revista: BIOLOGICAL & PHARMACEUTICAL BULLETIN
Volumen: 31
Número: 10
Editorial: PHARMACEUTICAL SOC JAPAN
Fecha de publicación: 2008
Página de inicio: 1911
Página final: 1916
Idioma: English
URL: http://joi.jlc.jst.go.jp/JST.JSTAGE/bpb/31.1911?from=CrossRef
DOI:

10.1248/bpb.31.1911

Notas: ISI, SCOPUS