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Micronutrient and Urate Transport in Choroid Plexus and Kidney: Implications for Drug Therapy
Authors:Reynold Spector  Conrad Johanson
Institution:(1) Robert Wood Johnson Medical School, New Brunswick, NJ, USA;(2) Harvard-MIT Program in the Health Sciences, Cambridge, MA, USA;(3) Brown Medical School, Providence, RI, USA;(4) Dept. of Neurosurgery, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
Abstract:Abstract 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.
Keywords:ascorbic acid  blood–  brain barrier  blood–  cerebrospinal fluid (CSF) barrier  choroid plexus epithelium  folate  folate receptor (FRα  )  inositol                  myo-inositol cotransporter (SMIT 1)  organic acid transporter 3 (OAT 3)  penicillin  riboflavin  sodium ascorbate cotransporter (SVCT 2)  uric acid transporter (URAT 1)  vitamin homeostasis
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