Blood-brain barrier transport ofL-pipecolic acid in various rat brain regions

Blood-brain barrier transport ofL-[l-¹⁴C]pipecolic acid was studied in the rat by single intracarotid injection using³H₂O as a diffusible internal standard. Brain uptake index (BUI) forL-[¹⁴C]pipecolic acid (0.036 mM) was found to be 18.1, 10.5, and 12.6 for the cerebral cortex, brain stem, and cerebellum, respectively which was substantially higher than that reported for its analogL-proline in the whole brain. Influx ofL-pipecolic acid into the brain was concentration dependent and differed significantly between the cerebral cortex and the brain stem, and between the cerebral cortex and the cerebellum, but not between the brain stem and the cerebellum. Kinetic study ofL-pipecolic acid influx revealed a low- and a high-capacity uptake mechanisms. The low-capacity saturable component hasK _m values ranging from 38 to 73 μM, andV _max values ranging from 10 to 13 nmol/g/min for the three brain regions. The nonsaturable component has aK _m of 4 mM, aV _max of 200 nmol/g/min and similar diffusion constant (K _d) (0.03 to 0.06 mlg^?1 min^?1) for all three brain regions. A possible role of the two-component brain uptake mechanism in the regulation of the neuronal function ofL-pipecolic acid was suggested.