Effects of 2,4,5-trichlorophenoxyacetic acid and quinolinic acid on 5-hydroxy-3-indoleacetic acid transport by the rabbit choroid plexus: pharmacology and electron microscopic cytochemistry.
2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) reduced the uptake of 5-hydroxy-3-indoleacetic acid (5-HIAA) by the choroid plexus in a dose-related manner, while treatment with quinolinic acid at comparable concentrations did not inhibit 5-HIAA uptake. The role of carrier-mediated transport in the clearance of 5-HIAA from cerebrospinal fluid (CSF) was also evaluated in vivo by ventriculocisternal perfusion. Steady-state clearance of 5-HIAA from CSF exceeded that of inulin and was reduced competitively in the presence of 2,4,5-T. However, the clearance was not affected by quinolinic acid. The effect of 2,4,5-T on transport enzyme systems was also studied by electron microscopic cytochemistry. Na+-K+-ATPase and cytochrome oxidase activities in the choroid plexus were reduced by 2,4,5-T. Since this transport system in the choroid plexus is normally responsible for the excretion of the serotonin metabolite from the brain to the plasma, accumulation of endogenously produced organic acids in the CSF and the brain, secondary to reduced clearance by the choroid plexus, could be a contributing factor in the development of neurotoxicity.
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002331:Carnitine / Q000494:pharmacology; D002831:Choroid Plexus / Q000187:drug effects / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000032:analysis; D005260:Female; D006651:Histocytochemistry; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D008657:Metabolic Clearance Rate; D008854:Microscopy, Electron; D011725:Pyridines / Q000633:toxicity*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis
D011725:Pyridines; D011805:Quinolinic Acids; D006897:Hydroxyindoleacetic Acid; D015085:2,4,5-Trichlorophenoxyacetic Acid; D003576:Electron Transport Complex IV; D000254:Sodium-Potassium-Exchanging ATPase; D017378:Quinolinic Acid; D002331:Carnitine