Abstract
The subarachnoid space, where CSF flows over the brain and spinal cord, is lined on one side by arachnoid barrier (AB) cells that form part of the blood-cerebrospinal fluid (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 junction AB cells have never been examined for whether they express drug transporters that would influence CSF and CNS drug disposition. Hence, we characterized drug transporter expression and function in AB cells. Immunohistochemical analysis showed P-glycoprotein (Pgp) and BCRP in mouse AB cells, but not other meningeal tissue. The Gene Expression Nervous System Atlas (GENSAT) database and the mouse Allen 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 Pgp on the apical (dura facing) membrane and BCRP on both apical and basal (CSF facing) membranes. Thus, like blood brain barrier (BBB) cells and choroid plexus (CP) cells, AB cells highly express drug transport proteins and likely contribute to the blood-CSF drug permeation barrier.
- Received November 26, 2012.
- Accepted January 8, 2013.
- The American Society for Pharmacology and Experimental Therapeutics