The transport of leucine and aminocyclopentanecarboxylate across the intact, energy-depleted rat blood-brain barrier.
The transport across the blood-brain barrier of the large neutral amino acid leucine and the nonmetabolised aminocyclopentanecarboxylate (ACPC), of similar molecular size, was studied in the perfused, energy-depleted rat brain. It was found that when both leucine and ACPC were perfused for periods of up to 10 min their accumulation in the brain increased in a linear fashion. The ratio of perfusate radioactivity per milliliter and tissue radioactivity per gram (Rt/Rp) rose to above unity for both leucine and ACPC, indicating continued uptake against a concentration gradient of the radiolabel within the CNS. When the effect of increasing the concentration of the amino acid upon its influx into the brain was studied, it was found that under these conditions the kinetics of transport for both leucine and ACPC were of a similar order of magnitude to those reported previously in vivo. The values for the Michaelis constant for transport (Km), maximum rate of transport (Vmax), and the constant for the apparently linear, nonsaturable component (Kd) for leucine into the cerebrum were 84.5 +/- 29.0 microM, 45.5 +/- 1.5 nmole/min/g, and 2.62 +/- 0.15 microliters/min/g, respectively, and for ACPC 381 +/- 64 microM, 54.0 +/- 1.5 nmole/min/g and 0.35 +/- 0.10 microliter/min/g, respectively. Comparing this data with previously reported values it is suggested that the transport of leucine into the central nervous system from a perfusate or bolus where no other competing amino acids are present, is flow dependent. Furthermore, ACPC enters the brain almost entirely by a carrier-mediated process, with little or no nonsaturable influx despite a similar oil/water partition coefficient as leucine.
Greenwood
J
J
Department of Neuropathology, Institute of Psychiatry, DeCrespigny Park, London, United Kingdom.
Hazell
A S
AS
Pratt
O E
OE
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier; D003515:Cycloleucine / Q000378:metabolism*; D004734:Energy Metabolism; D007930:Leucine / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D003515:Cycloleucine; D007930:Leucine