Micronutrient and urate transport in choroid plexus and kidney: implications for drug therapy.
With application of molecular biology techniques, there has been rapid progress in understanding how many drugs and micronutrients (e.g., vitamins) are transferred across the choroid plexus (CP), the main transport locus of the blood-cerebrospinal fluid (CSF) barrier, and the renal tubular epithelial cells. In many cases, these molecules are transported by separate, specific carriers or receptors on the apical and/or basal side of the CP or renal epithelial cells. This commentary focuses on four micronutrient transport systems in CP (ascorbic acid, folate, inositol, and riboflavin), all of which have been recently cloned, expressed and for which knockout mice models were developed and transporter localization studies performed. Also reviewed is the recently cloned uric acid transport system in human kidney in which there exists a human "knockout" model. The implications of these transport systems for drug therapy of central nervous system and renal disorders are discussed, especially with regard to methods to circumvent the blood-brain and blood-CSF barriers to deliver drugs to the brain.
Spector
Reynold
R
Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Johanson
Conrad
C
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002831:Choroid Plexus / Q000378:metabolism*; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000502:physiology; D029362:Organic Anion Transporters, Sodium-Independent / Q000502:physiology; D027701:Organic Cation Transport Proteins / Q000502:physiology; D012256:Riboflavin / Q000378:metabolism*; D014527:Uric Acid / Q000378:metabolism*
D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C114338:organic anion transport protein 3; D014527:Uric Acid; D007294:Inositol; D005492:Folic Acid; D001205:Ascorbic Acid; D012256:Riboflavin