Phenylalanine transport at the human blood-brain barrier. Studies with isolated human brain capillaries.
The exquisite sensitivity of brain amino acid availability to changes in plasma amino acid composition arises from the uniquely high affinity (low Km) of blood-brain barrier transport sites as compared to cell membrane transport systems in nonbrain tissues. The extension of this paradigm from rats to man assumes that the Km of blood-brain barrier amino acid transport in the human is low as in the rat. This hypothesis is tested in the present studies wherein isolated human brain capillaries are used as a model system for the human blood-brain barrier. Capillaries were obtained from autopsy brain between 20 and 45 h after death and were isolated in high yield and free of adjoining brain tissue. [3H]Phenylalanine transport into the isolated human, rabbit, or rat brain capillary was characterized by two saturable transport systems and a nonsaturable component. The Km values of phenylalanine transport into brain capillaries via the two saturable systems averaged 0.26 +/- 0.08 and 22.3 +/- 7.1 microM for five human subjects. These studies provide the first evidence for a very high affinity (Km = 0.26 microM) neutral amino acid transport system at the blood-brain barrier, and it is hypothesized that this system is selectively localized to the brain side of the blood-brain barrier. The results also show that the transport Km values for phenylalanine transport are virtually identical at both the rat and human blood-brain barrier.
T B
TB
Choi
W M
WM
Pardridge
D000328:Adult; D000368:Aged; D000818:Animals; D001693:Biological Transport, Active; D001812:Blood-Brain Barrier; D002196:Capillaries / Q000378:metabolism; D002560:Cerebrovascular Circulation; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D010649:Phenylalanine / Q000378:metabolism*; D011817:Rabbits; D014443:Tyrosine / Q000378:metabolism
D014443:Tyrosine; D010649:Phenylalanine