title: Drug transporters on arachnoid barrier cells contribute to the blood-cerebrospinal fluid barrier.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, USA.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Yasuda
authors.forename: Cynthia
authors.initials: C
authors.lastname: Cline
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Mihaela
authors.initials: M
authors.lastname: Onciu
authors.forename: Soghra
authors.initials: S
authors.lastname: Fatima
authors.forename: Brian P
authors.initials: BP
authors.lastname: Sorrentino
authors.forename: Ranjit K
authors.initials: RK
authors.lastname: Thirumaran
authors.forename: Sean
authors.initials: S
authors.lastname: Ekins
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Ko
authors.initials: K
authors.lastname: Fujimori
authors.forename: Erin G
authors.initials: EG
authors.lastname: Schuetz
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001099:Arachnoid / Q000166:cytology*; D001692:Biological Transport / Q000235:genetics; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D015870:Gene Expression; D000882:Haplorhini; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D009363:Neoplasm Proteins