CEREBRAL PASSAGE OF FREE AMINO ACIDS 501 
In similar experiments with the D-isomers the results were parallel to those with 
the L-forms in that the rate of exit varied from one amino acid to another and the 
efflux rates of the three compounds were in decreasing order: leucine > phenyl- 
alanine > lysine (Table IV). 
From the data presented in Tables III and IV the relative rates of efflux can be 
calculated. These are presented (Table V) as half times (time required for the brain 
level to decrease to half), and the two isomers are compared. The ratio of the relative 
exit rate of the two isomers (D over L) was highest in the case of leucine, lower in the 
case of lysine, and close to unity in the case of phenylalanine. It is of interest that 
these ratios—an indication in a sense of the stereospecificity of the efflux—showed 
the same relationship as did the relative transport against a concentration gradient 
TABLE V 
RELATIVE EFFLUX RATES OF L- AND D-AMINO ACIDS FROM RAT BRAIN 

Minutes for 50% decrease in level* 




Leucine Phenylalanine Lysine 
Time intervals minutes : : ae = : 
L D L D L D 
5= 45 14 28 
20-120 27 32 
45-240 140 200 
Ratio D/L 2.0 Te 1.4 

* time interval in minutes 

°% loss during interval 
from the brain, where the leucine pump was more efficient than the lysine pump 
and no phenylalanine pump could be shown. This parallelism suggest, that stereo- 
specificity is a property of the active transport process. 
The differences in efflux rates between the two isomers, however, do not exclude 
the possibility that the transport of the p-forms can also be mediated. This possibility 
has to be taken into consideration because of the finding of accumulation of D- 
glutamic acid against a concentration gradient in brain slices**. At present experi- 
ments are being conducted in our laboratory to test 7m vivo D-amino acid transport 
from the brain against a concentration gradient®?. 
An indication that the passage of the two isomers of the amino acids is not com- 
pletely independent is the finding of increased content of the L-amino acid in the 
brain following the administration of the p-form?®. Since in a number of other ex- 
periments no racemization of the D-form was found, the most likely explanation for 
this finding is that some of the p-form in the brain was replaced by the L-form 
through exchange, that is, that the exchange mechanism of the L-form has some 
affinity for the D-form. 
A net decrease in the content of the p-form in the brain thus occurs through net 
outflow and through exchange (replacement by the L-form), while a net decrease in 
the content of the L-form occurs through net outflow only. (It cannot be excluded 
References p. 563 
