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.