| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, NC, USA
2 Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, SC, USA
3 Departments of Pediatrics and Medicine, Division of Nephrology/Hypertension, University of California, San Diego, La Jolla, CA, USA
* To whom correspondence should be addressed. E-mail: miller{at}niehs.nih.gov.
The choroid plexus actively transports endogenous, xenobiotic, and therapeutic compounds from cerebrospinal fluid to blood, thereby limiting their exposure to the central nervous system (CNS). Establishing the mechanisms responsible for this transport is critical to our understanding of basic choroid plexus physiology and will likely impact drug targeting to the CNS. We recently generated an organic anion transporter 3- (Oat3)-null mouse, which exhibited loss of p-aminohippurate (PAH), estrone sulfate, and taurocholate transport in kidney and of fluorescein (FL) transport in choroid plexus. Here we measured the uptake of four Oat3 substrates by choroid plexus from wild-type and Oat3-null mice to establish 1) the contribution of Oat3 to the apical uptake of each substrate, and 2) the Na-dependence of transport by Oat3 in the intact tissue. Mediated transport of PAH and FL was essentially abolished in tissue from Oat3-null mice. In contrast, only a 33% reduction in estrone sulfate uptake was observed in tissue from Oat3-null mice and, surprisingly, no reduction in taurocholate uptake could be detected. For PAH, FL and estrone sulfate, all Oat3-mediated transport was Na-dependent. However, estrone sulfate and taurocholate also exhibited additional mediated and Na-dependent components of uptake that were not attributed to Oat3, demonstrating the complexity of organic anion transport in this tissue and the need for further examination of expressed transporters and their energetics.
This article has been cited by other articles:
|
|
 |
|
  V. Reichel, D. S. Miller, and G. Fricker Texas Red transport across rat and dogfish shark (Squalus acanthias) choroid plexus Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2008; 295(4): R1311 - R1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Baehr, G. Fricker, and D. S. Miller Fluorescein-methotrexate transport in dogfish shark (Squalus acanthias) choroid plexus Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R464 - R472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Silva, S. Dasgupta, G. Wang, K. Krishnamurthy, E. Ritter, and E. Bieberich Lipids isolated from bone induce the migration of human breast cancer cells J. Lipid Res., April 1, 2006; 47(4): 724 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Breen, D. B. Sykes, C. Baehr, G. Fricker, and D. S. Miller Fluorescein-methotrexate transport in rat choroid plexus analyzed using confocal microscopy Am J Physiol Renal Physiol, September 1, 2004; 287(3): F562 - F569. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
