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Kinetics of Neutral Amino Acid Transport Across the Blood‐Brain Barrier
Author(s) -
Smith Quentin R.,
Momma Seiji,
Aoyagi Masaki,
Rapoport Stanley I.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb01039.x
Subject(s) - chemistry , amino acid , partition coefficient , blood–brain barrier , kinetics , octanol , stereochemistry , chromatography , biochemistry , central nervous system , endocrinology , biology , physics , quantum mechanics
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 ( V max , K m , K D ) were determined for seven large NAAs from saturation studies, whereas K m values 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, V max varied at least fivefold and K m varied ∼700 fold. The apparent affinity (1/ K m ) 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.