Transport of Tryptophan into Brain from the Circulating, Albumin‐Bound Pool in Rats and in Rabbits

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Abstract
Tryptophan is the only amino acid in the circulation that is bound by albumin, and previous studies have suggested that the brain tryptophan supply is a function of either the free or the albumin-bound pool of tryptophan in blood. Since the albumin molecule per se does not cross the brain capillary wall, i.e., the blood-brain barrier (BBB), the transport of tryptophan from the circulating albumin-bound pool may involve enhanced dissociation of tryptophan from the albumin binding sites within the cerebral microcirculation. This hypothesis was confirmed in the present studies wherein the dissociation constant (KaD) of albumin binding of tryptophan in the rat or rabbit brain microcirculation was measured in vivo. Brain extraction data for [14C]tryptophan determined with the carotid artery injection technique were fit to the Kety-Renkin-Crone equation modified for protein-bound solute. The KaD of albumin binding in the rat or rabbit brain microcirculation under pentobarbital anesthesia was 1.7 ± 0.1 and 3.9 ± 1.0 mM, respectively, as compared to the KD value measured in vitro with equilibrium dialysis, 0.13 ± 0.03 mM. In contrast, the KaD value of albumin binding of tryptophan in vivo in the rabbit brain microcirculation was reduced by ether anesthesia to value of 2.1 ± 0.4 mM. This reduction in the KaD under ether anesthesia was associated with a 2.5-fold increase in cerebral blood flow. In addition, dialyzed rabbit serum caused a statistically significant inhibition in [14C]tryptophan influx during ether, but not pentobarbital, anesthesia. The BBB permeability-surface area product (PS) was estimated along with the KaD parameter, and this PS value in the rabbit brain, 0.13 ml/min/g, was identical to the quantity [(Vmax/Km) +KD] measured from estimates of the constants of saturable (Km, Vmax) and nonsaturable (KD) transport of tryptophan through the BBB. In conclusion, the present studies demonstrate that tryptophan is transported into brain from the circulating albumin-bound pool via an enhanced dissociation mechanism and that this process varies among species and with changing anesthesia and cerebral hemodynamics.