Phenylalanine transport across the blood-brain barrier as studied with the in situ brain perfusion technique

J Neurochem. 1987 Apr;48(4):1291-300. doi: 10.1111/j.1471-4159.1987.tb05660.x.

Abstract

Unidirectional L-phenylalanine transport into six brain regions of pentobarbital-anesthetized rats was studied using the in situ brain perfusion technique. This technique allows both accurate measurements of cerebrovascular amino acid transport and complete control of perfusate amino acid composition. L-Phenylalanine influx into the brain was sodium independent and could be described by a model with a saturable and a nonsaturable component. Best-fit values for the kinetic constants in the parietal cortex equaled 6.9 X 10(-4) mumol/s/g for Vmax, 0.011 mumol/ml for Km, and 1.8 X 10(-4) ml/s/g for KD during perfusion with fluid that did not contain competing amino acids. D-Phenylalanine competitively inhibited L-phenylalanine transport with a Ki approximately 10-fold greater than the Km for L-phenylalanine. There were no significant regional differences in Km, KD, or Ki, whereas Vmax was significantly greater in the cortical lobes than in the other brain regions. L-Phenylalanine influx during plasma perfusion was only 30% of that predicted in the absence of competing amino acids. Competitive inhibition increased the apparent Km during plasma perfusion by approximately 20-fold, to 0.21 mumol/ml. These data provide accurate new estimates of the kinetic constants that describe L-phenylalanine transport across the blood-brain barrier. In addition, they indicate that the cerebrovascular transfer site affinity (1/Km) for L-phenylalanine is three- to 12-fold greater than previously estimated in either awake or anesthetized animals.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acids / blood
  • Animals
  • Antipyrine / analogs & derivatives
  • Antipyrine / metabolism
  • Biological Transport
  • Blood-Brain Barrier*
  • Brain / blood supply
  • Brain / metabolism*
  • Capillary Permeability
  • Caudate Nucleus / metabolism
  • Hippocampus / metabolism
  • Kinetics
  • Male
  • Parietal Lobe / metabolism
  • Perfusion
  • Phenylalanine / blood
  • Phenylalanine / metabolism*
  • Rats
  • Sodium Chloride
  • Solutions
  • Sucrose

Substances

  • Amino Acids
  • Solutions
  • Sodium Chloride
  • Phenylalanine
  • Sucrose
  • Antipyrine
  • iodoantipyrine