Vectorial ligand transport through mammalian choroid plexus

Abstract

In the last decade, there has been substantial progress in understanding vectorial ligand transport through rodent and human choroid plexus (CP), the locus of the blood-CSF interface. In this Review, we enumerate the experimental data required to establish vectorial transport through CP and describe transporters involved in vectorial transport across CP. We also note how these transporters differ from those at the blood-brain barrier. The ligand (substrate) examples presented are methyltetrahydrofolate, methotrexate, leukotriene C(4), nucleosides, thiamine monophosphate, prostaglandins, and digoxin. Our focus is on more definitive experiments, including animal and human transporter "knock-outs." Finally, we discuss the neurochemical implications of vectorial transport through CP and the clinical implications of transporter polymorphisms and knockouts. Examples include descriptions of how vectorial transport through the CP for several micronutrients (e.g., methyltetrahydrofolate) nourishes the brain and how knowledge of CP vectorial transport can lead to important treatments.