Transport of 2,4,5-trichlorophenoxyacetic acid across the blood-cerebrospinal fluid barrier of the rabbit.
Transport of the anionic herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) across the blood-cerebrospinal fluid barrier was investigated using the isolated choroid plexus of the adult rabbit in vitro and ventriculocisternal perfusion in vivo. In vitro, 2,4,5-T transport was effective, with tissue concentrations 20 times those in the medium after only 5 min of incubation with 1 microM 2,4,5-T. The tissue to medium ratios reached steady state by 20 min at approximately 45-fold. Uptake was energy dependent and inhibited by ouabain, phloridzin and several organic anions (probenecid, 2,4-dichlorophenoxyacetic acid and octanoate). Neither tyrosine (transported by a separate system) nor the neurotoxin, quinolinic acid, inhibited 2,4,5-T transport. Kinetic analysis yielded an apparent Km of 58 microM and Vmax of 111 nmol g-1 min-1 in the lateral ventricular choroid plexus with similar values (57 microM and 87 nmol g-1 min-1) in the fourth ventricular plexus. In vivo, the steady-state clearance of 2,4,5-T from the cerebrospinal fluid exceeded that of inulin and was reduced in a dose-dependent fashion by 2,4-dichlorophenoxyacetic acid and probenecid. Together, these data indicate that 2,4,5-T is cleared from the brain and cerebrospinal fluid by the organic anion transport system and that alterations in such transport may have a significant impact on the toxicity of this agent in the central nervous system.
Kim
C S
CS
Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill.
Pritchard
J B
JB
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics* / Q000633:toxicity; D015084:2,4-Dichlorophenoxyacetic Acid / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D002831:Choroid Plexus / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D010695:Phlorhizin / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D011817:Rabbits
D015084:2,4-Dichlorophenoxyacetic Acid; D010042:Ouabain; D015085:2,4,5-Trichlorophenoxyacetic Acid; D010695:Phlorhizin; D011339:Probenecid