Texas Red transport across rat and dogfish shark (Squalus acanthias) choroid plexus.
Confocal microscopy and image analysis were used to compare driving forces, specificity, and regulation of transport of the fluorescent organic anion, Texas Red (sulforhodamine 101 free acid; TR), in lateral choroid plexus (CP) isolated from rat and an evolutionarily ancient vertebrate, dogfish shark (Squalus acanthias). CP from both species exhibited concentrative, specific, and metabolism-dependent TR transport from bath to subepithelial/vascular space; at steady state, TR accumulation in vascular/subepithelial space was substantially higher than in epithelial cells. In rat CP, steady-state TR accumulation in subepithelial/vascular spaces was reduced by Na(+)-replacement, but was not affected by a 10-fold increase in buffer K(+). In shark CP, Na(+)-replacement did not alter TR accumulation in either tissue compartment; subepithelial/vascular space levels of TR were reduced in high-K(+) medium. In both species, steady-state TR accumulation was not affected by p-aminohippurate or leukotriene C4, suggesting that neither organic anion transporters (SLC22A family) nor multidrug resistance-associated proteins (ABCC family) contributed. In rat CP, digoxin was without effect, indicating that organic anion transporting polypeptide isoform 2 was not involved. Several organic anions reduced cellular and subepithelial/vascular space TR accumulation in both tissues, including estrone sulfate, taurocholate, and the Mrp1 inhibitor MK571. In rat CP, TR accumulation in subepithelial/vascular spaces increased with PKA activation (forskolin), but was not affected by PKC activation (phorbol ester). In shark, neither PKA nor PKC activation specifically affected TR transport. Thus, rat and dogfish shark CP transport TR but do so using different basic mechanisms that respond to different regulatory signals.
Reichel
Valeska
V
Institute of Pharmacy and Molecular Biotechnology, INF 366, 69120 Heidelberg, Germany.
Miller
David S
DS
Fricker
Gert
G
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002831:Choroid Plexus / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D007700:Kinetics; D017997:Leukotriene C4 / Q000494:pharmacology; D008297:Male; D008536:Meglumine / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D008954:Models, Biological; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D011188:Potassium / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012966:Sodium Cyanide / Q000494:pharmacology; D048251:Squalus acanthias / Q000378:metabolism*; D013656:Taurocholic Acid / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014966:Xanthenes / Q000378:metabolism / Q000493:pharmacokinetics*; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D027361:Organic Anion Transporters; D011422:Propionates; D011804:Quinolines; D014966:Xanthenes; D005576:Colforsin; D017997:Leukotriene C4; D004970:Estrone; D013656:Taurocholic Acid; C059141:verlukast; D008536:Meglumine; C034657:Texas red; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D012966:Sodium Cyanide; C017296:estrone sulfate; D011188:Potassium; D010130:p-Aminohippuric Acid; D008727:Methotrexate