RT Journal Article
SR Electronic
T1 Drug Transporters on Arachnoid Barrier Cells Contribute to the Blood–Cerebrospinal Fluid Barrier
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 923
OP 931
DO 10.1124/dmd.112.050344
VO 41
IS 4
A1 Kazuto Yasuda
A1 Cynthia Cline
A1 Peter Vogel
A1 Mihaela Onciu
A1 Soghra Fatima
A1 Brian P. Sorrentino
A1 Ranjit K. Thirumaran
A1 Sean Ekins
A1 Yoshihiro Urade
A1 Ko Fujimori
A1 Erin G. Schuetz
YR 2013
UL http://dmd.aspetjournals.org/content/41/4/923.abstract
AB The subarachnoid space, where cerebrospinal fluid (CSF) flows over the brain and spinal cord, is lined on one side by arachnoid barrier (AB) cells that form part of the blood-CSF barrier. However, despite the fact that drugs are administered into the CSF and CSF drug concentrations are used as a surrogate for brain drug concentration following systemic drug administration, the tight-junctioned AB cells have never been examined for whether they express drug transporters that would influence CSF and central nervous system drug disposition. Hence, we characterized drug transporter expression and function in AB cells. Immunohistochemical analysis showed P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) in mouse AB cells but not other meningeal tissue. The Gene Expression Nervous System Atlas (GENSAT) database and the Allen Mouse Brain Atlas confirmed these observations. Microarray analysis of mouse and human arachnoidal tissue revealed expression of many drug transporters and some drug-metabolizing enzymes. Immortalized mouse AB cells express functional P-gp on the apical (dura-facing) membrane and BCRP on both apical and basal (CSF-facing) membranes. Thus, like blood-brain barrier cells and choroid plexus cells, AB cells highly express drug transport proteins and likely contribute to the blood-CSF drug permeation barrier.