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Kinetics of Neutral Amino Acid Transport Across the Blood-Brain Barrier

Authors

  • Quentin R. Smith,

    Corresponding author
    1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, U.S.A.
      Address correspondence and reprint requests to Dr. Q. R. Smith at Laboratory of Neurosciences, National Institute on Aging, NIH, Bldg. 10, Room 6C103, Bethesda, MD 20892, U.S.A.
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  • Seiji Momma,

    1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, U.S.A.
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  • Masaki Aoyagi,

    1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, U.S.A.
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  • Stanley I. Rapoport

    1. Laboratory of Neurosciences, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, U.S.A.
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  • Portions of this work were presented at the Symposium on the Blood-Brain Barrier, in Copenhagen, Denmark, June 20–22, 1985, and at the UCLA Symposium, Amino Acids in Health and Disease: New Perspectives, in Keystone, Colorado, May 30-June 4, 1986.

Address correspondence and reprint requests to Dr. Q. R. Smith at Laboratory of Neurosciences, National Institute on Aging, NIH, Bldg. 10, Room 6C103, Bethesda, MD 20892, U.S.A.

Abstract

Abstract: Neutral amino acid (NAA) transport across the blood-brain barrier was examined in pentobarbital-anesthetized rats with an in situ brain perfusion technique. Fourteen of 16 plasma NAAs showed measurable affinity for the cerebrovascular NAA transport system. Values of the transport constants (Vmax, Km, KD) were determined for seven large NAAs from saturation studies, whereas Kmvalues for five small NAAs were estimated from inhibition studies. These data, together with our previous work, provide a complete set of constants for prediction of NAA influx from plasma. Among the NAAs, Vmax varied at least fivefold and Km varied ∼700 fold. The apparent affinity (1/Km) of each NAA was related linearly (r= 0.910) to the octanol/water partition coefficient, a measure of NAA side-chain hydrophobicity. Predicted influx values from transport constants and average plasma concentrations agree well with values measured using plasma perfusate. These results provide accurate new estimates of the kinetic constants that determine NAA transport across the Mood-brain barrier. Furthermore, they suggest that affinity of a l-α-amino acid for the transport system is determined primarily by side-chain hydrophobicity.

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