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Choroid Plexus Pharmacology
Functional and Molecular Aspects of Xenobiotic Transport
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The choroid plexus (CP) epithelium forms theblood-cerebrospinal fluid (CSF) barrier and, along with theblood-brain barrier, maintains the fluid environment of the brain.The CP not only secretes CSF, but also transports potentially toxicxenobiotics and waste products of neural metabolism to the bloodfor eventual clearance in kidney and liver. However, studying CP isdifficult, due to complex morphology, anatomical location and smallsize of the tissue and little is known about the molecularmechanisms, functional complexity and hormonal regulation oforganic anion secretion. To further elucidate the underlyingmechanisms of organic anion transport across CP epithelium, aprimary porcine CP cell culture model was established andcharacterized. Organic anion transport was studied in a mammalian(rat), a comparative elasmobranch and in an in vitro porcine cellculture model, using model compound fluorescein-methotrexate.Organic anion transport was shown to be a specific andconcentrative, Na-ion dependent and metabolism-dependent two-stepprocess. Finally, for the first time, the studies demonstrated thatorganic anion transport is regulated by protein kinase (PK) C andPKA.
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