Blood-Brain Barrier Transport of 1-Aminocyclohexanecarboxylic Acid, a Nonmetabolizable Amino Acid for In Vivo Studies of Brain Transport
1988
: Regional transport of 1-aminocyclohexanecarboxylic acid (ACHC), a nonmetabolizable amino acid, across the blood-brain barrier was studied in pentobarbital-anesthetized rats using an in situ brain perfusion technique. The concentration dependence of influx was best described by a model with a saturable and a nonsaturable component. Best-fit values for the kinetic constants of the frontal cortex equaled 9.7 × 10-−4μmol/s/g for Vmax, 0.054 μmol/ml for Km, and 1.0 × 10-−4 ml/s/g for KD in the absence of competing amino acids. Saturable influx could be reduced by >85% by either l-phenylalanine or 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid, consistent with transport by the cerebrovascular neutral amino acid transport system. The transport Km for ACHC was one-fifth that for the more commonly used homologue, I-aminocyclopentanecarboxylic acid, and was similar to values for several natural amino acids, such as l-methionine, l-isoleucine, and l-tyrosine. The results indicate that ACHC may be a useful probe for in vivo studies of amino acid transport into brain.
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