Excretory transport of xenobiotics by dogfish shark rectal gland tubules.
Marine elasmobranch rectal gland is a specialized, osmoregulatory organ composed of numerous blind-ended, branched tubules emptying into a central duct. To date, NaCl excretion has been its only described function. Here we use isolated rectal gland tubule fragments from dogfish shark (Squalus acanthias), fluorescent xenobiotics, and confocal microscopy to describe a second function, xenobiotic excretion. Isolated rectal gland tubules rapidly transported the fluorescent organic anion sulforhodamine 101 from bath to lumen. Luminal accumulation was concentrative, saturable, and inhibited by cyclosporin A (CSA), chlorodinitrobenzene, leukotriene C4, and KCN. Inhibitors of renal organic anion transport (probenecid, p-aminohippurate), organic cation transport (tetraethylammonium and verapamil), and P-glycoprotein (verapamil) were without effect. Cellular accumulation of sulforhodamine 101 was not concentrative, saturable, or inhibitable. Rectal gland tubules did not secrete fluorescein, daunomycin, or a fluorescent CSA derivative. Finally, frozen rectal gland sections stained with an antibody to a hepatic canalicular multispecific organic anion transporter (cMOAT or MRP2) showed heavy and specific staining on the luminal membrane of the epithelial cells. We conclude that rectal gland is capable of active and specific excretion of xenobiotics and that such transport is mediated by a shark analog of MRP2, an ATP-driven xenobiotic transporter, but not by P-glycoprotein.
Miller
D S
DS
Intracellular Regulation Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Masereeuw
R
R
Henson
J
J
Karnaky
K J
KJ
D000818:Animals; D001692:Biological Transport; D016572:Cyclosporine / Q000494:pharmacology; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004284:Dogfish / Q000378:metabolism*; D005260:Female; D005456:Fluorescent Dyes; D017997:Leukotriene C4 / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D011190:Potassium Cyanide / Q000494:pharmacology; D012235:Rhodamines / Q000378:metabolism; D012491:Salt Gland / Q000378:metabolism*; D015262:Xenobiotics / Q000378:metabolism*
D004137:Dinitrochlorobenzene; D005456:Fluorescent Dyes; D012235:Rhodamines; D015262:Xenobiotics; D017997:Leukotriene C4; D016572:Cyclosporine; C050829:sulforhodamine 101; D011190:Potassium Cyanide