Choroid Plexus Pharmacology: Functional and Molecular Aspects of Xenobiotic Transport

The choroid plexus (CP) epithelium forms the blood-cerebrospinal fluid (CSF) barrier and, along with the blood-brain barrier, maintains the fluid environment of the brain. The CP not only secretes CSF, but also transports potentially toxic xenobiotics and waste products of neural metabolism to the blood for eventual clearance in kidney and liver. However, studying CP is difficult, due to complex morphology, anatomical location and small size of the tissue and little is known about the molecular mechanisms, functional complexity and hormonal regulation of organic anion secretion. To further elucidate the underlying mechanisms of organic anion transport across CP epithelium, a primary porcine CP cell culture model was established and characterized. Organic anion transport was studied in a mammalian (rat), a comparative elasmobranch and in an in vitro porcine cell culture model, using model compound fluorescein-methotrexate. Organic anion transport was shown to be a specific and concentrative, Na-ion dependent and metabolism-dependent two-step process. Finally, for the first time, the studies demonstrated that organic anion transport is regulated by protein kinase (PK) C and PKA.