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Am J Physiol Regul Integr Comp Physiol 282: R1308-R1316, 2002. First published January 17, 2002; doi:10.1152/ajpregu.00677.2001
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Vol. 282, Issue 5, R1308-R1316, May 2002

Transepithelial organic anion transport by shark choroid plexus

Alice R. A. Villalobos1,2, David S. Miller1,3, and J. Larry Renfro1,4

1 Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672; 2 Department of Environmental Medicine, University of Rochester, Rochester, New York 14642; 3 Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; and 4 Department of Physiology and Neurobiology, University of Connecticut-Storrs, Storrs, Connecticut 06269

Spiny dogfish shark (Squalus acanthias) lateral and IV choroid plexuses (CPs) are ultrastructurally similar to the corresponding tissues of rat. However, shark IV CP is proportionally larger and easily accessible. Moreover, this epithelial sheet can be halved and studied in Ussing flux chambers. We have used confocal fluorescence microscopy and radiotracer techniques to characterize transepithelial transport of the organic anions (OAs) fluorescein (FL) and 2,4-dichlorophenoxyacetic acid (2,4-D), respectively, by shark CP. Lateral and IV CP accumulated 1 µM FL, with highest levels in the underlying extracellular spaces, intermediate levels in epithelial cells, and lowest levels in the medium. 2,4-D and probenecid inhibited FL accumulation in cells and extracellular spaces, suggesting that these substrates compete for common carriers. Unidirectional absorptive [cerebrospinal fluid (CSF)-to-blood] and secretory (blood-to-CSF) fluxes of 10 µM [14C]2,4-D were measured under short-circuited conditions in IV CP mounted in Ussing chambers. 2,4-D underwent net absorption, with an average flux ratio of 7. Probenecid, 2,4,5-trichlorophenoxyacetic acid, and 5-hydroxyindolacetic acid reduced net absorption, reversibly inhibiting unidirectional absorption, with no effect on secretion. Ouabain irreversibly reduced net 2,4-D absorption and cellular and extracellular accumulation of FL, suggesting energetic coupling of OA absorption to Na+ transport. Collectively, these data indicate that shark CP actively removes OAs from CSF by a process that is specific and active.

blood-cerebrospinal fluid barrier; xenobiotic; 2,4-dichlorophenoxyacetic acid; dogfish; elasmobranch


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