Kinetics of Neutral Amino Acid Transport Through the Blood‐Brain Barrier of the Newborn Rabbit

Abstract

Since protein synthesis in the developing brain may, under certain conditions, be limited by amino acid availability, studies were undertaken to characterize the kinetics of large neutral amino acid transport through the blood-brain barrier (BBB) of the newborn rabbit. The Km, Vmax, and Kd of the transport of 8 amino acids were determined by a nonlinear regression analysis of data obtained with the carotid injection technique. Compared with kinetic parameters observed for the adult rat, the Km, Vmax, and Kd of amino acid transport were all 2- to 3-fold higher in the newborn. Albumin was found to bind tryptophan actively in vitro, but had no inhibitory effect on tryptophan transport through the newborn BBB. Glutamine was transported through the BBB of the newborn at rates severalfold higher than are seen in the adult rat. Glutamine transport was not inhibited by high concentrations of N-methylaminoisobutyric acid (NMAIB), a model amino acid that is specific for the alanine-preferring or A-system present in peripheral tissues. The BBB neutral amino acid transport system of the newborn rabbit has a lower affinity and higher capacity than does the BBB of the adult rat. Under conditions of high plasma amino acids, the increased capacity of the newborn transport system allows for a higher rate of amino acid transport into brain than would occur via the lower capacity system present in the adult rat brain.