Blood-brain barrier transport of 1-aminocyclohexanecarboxylic acid, a nonmetabolizable amino acid for in vivo studies of brain transport.
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 X 10(-4) mumol/s/g for Vmax, 0.054 mumol/ml for Km, and 1.0 X 10(-4) ml/s/g for KD in the absence of competing amino acids. Saturable influx could be reduced by greater than 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, 1-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.
Aoyagi
M
M
Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892.
Agranoff
B W
BW
Washburn
L C
LC
Smith
Q R
QR
D000596:Amino Acids / Q000378:metabolism* / Q000494:pharmacology; D000598:Amino Acids, Cyclic; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D003509:Cyclohexanecarboxylic Acids / Q000378:metabolism*; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013788:Thalamus / Q000378:metabolism
D000596:Amino Acids; D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; C014966:1-aminocyclohexanecarboxylic acid