Accumulation of anionic pesticides by rabbit choroid plexus in vitro.
In this study, two questions were addressed: 1) were anionic pesticides accumulated by choroid plexus via the organic acid transport system and 2) did such accumulation impair transport of anionic neurotransmitter metabolites normally eliminated from brain via this system? Rabbit lateral choroid plexi were incubated in Krebs-Ringer bicarbonate buffer in vitro with the herbicide, 2,4-dichlorophenoxyacetic acid, or the polar DDT metabolite, 2,2-bis (p-chlorophenyl)acetic acid (DDA). Both compounds were extensively accumulated. At a pesticide concentration of 1 microM, tissue-to-medium ratios of 40 (DDA) to 50 (2,4-dichlorophenoxyacetic acid) were found after 60-min incubation at 37 degrees C. Uptake of both compounds was energy- and concentration-dependent and could be inhibited by other organic anions. 2,4-Dichlorophenoxyacetic acid and DDA each produced dose-dependent inhibition of the uptake of the other pesticide. DDA was the more potent inhibitor. Thus, uptake of both compounds appeared to be mediated by the organic acid transport system. Furthermore, transport of the serotonin metabolite, 5-hydroxy-3-indole-acetic acid was more effectively inhibited by these pesticides than by the classical inhibitor, probenecid. Neither the parent amine, serotonin, nor the uncharged pesticides. DDT and dieldrin, inhibited 5-hydroxy-3-indole-acetic acid uptake. Thus, the effect appears specific for those compounds which share the organic anion transport system.
D015084:2,4-Dichlorophenoxyacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D000838:Anions; D001693:Biological Transport, Active; D002831:Choroid Plexus / Q000378:metabolism*; D003486:Cyanides / Q000494:pharmacology; D003634:DDT / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009584:Nitrogen / Q000494:pharmacology; D011485:Protein Binding; D011817:Rabbits; D014018:Tissue Distribution
D000838:Anions; D003486:Cyanides; D015084:2,4-Dichlorophenoxyacetic Acid; D006897:Hydroxyindoleacetic Acid; C000849:bis(p-chlorophenyl)acetic acid; D003634:DDT; D009584:Nitrogen