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Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain
Author(s) -
Soares Ricardo V.,
Do Tuan M.,
Mabondzo Aloïse,
Pons Gérard,
Chhun Stéphanie
Publication year - 2016
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12175
Subject(s) - efflux , transporter , abcg2 , atp binding cassette transporter , biology , blood–brain barrier , p glycoprotein , pharmacology , multidrug resistance associated protein 2 , gene expression , multidrug resistance associated proteins , microbiology and biotechnology , gene , solute carrier family , biochemistry , central nervous system , endocrinology , drug resistance , genetics , multiple drug resistance
Abstract The blood–brain barrier ( BBB ) is responsible for the control of solutes’ concentration in the brain. Tight junctions and multiple ATP ‐binding cassette ( ABC ) and SoLute Carrier ( SLC ) efflux transporters protect brain cells from xenobiotics, therefore reducing brain exposure to intentionally administered drugs. In epilepsy, polymorphisms and overexpression of efflux transporters genes could be associated with pharmacoresistance. The ontogeny of these efflux transporters should also be addressed because their expression during development may be related to different brain exposure to antiepileptic drugs in the immature brain. We detected statistically significant higher expression of Abcb1b and Slc16a1 genes, and lower expression of Abcb1a and Abcg2 genes between the post‐natal day 14 (P14) and the adult rat microvessels. P‐ gP efflux activity was also shown to be lower in P14 rats when compared with the adults. The P‐ gP proteins coded by rodent genes Abcb1a and Abcb1b are known to have different substrate affinities. The role of the Abcg2 gene is less clear in pharmacoresistance in epilepsy, nonetheless the coded protein Bcrp is frequently associated with drug resistance. Finally, we observed a higher expression of the Mct1 transporter gene in the P14 rat brain microvessels. Accordingly to our results, we suppose that age may be another factor influencing brain exposure to antiepileptics as a consequence of different expression patterns of efflux transporters between the adult and immature BBB.