558 A. LAJTHA 
in cerebral levels took longer as compared to leucine efflux, and the plasma to brain 
ratio reached was about 5—6. Under such experimental conditions and at two different 
plasma levels no decrease in the cerebral concentration of phenylalanine could be 
shown (Fig. 3). 
The above observations point out the two-directional nature of transport mecha- 
nisms and consequently of the control of cerebral metabolite levels. Substrate levels 
in the brain can be kept below that of the plasma by a barrier to entry, by an ex- 
change in which upon entry an equivalent amount passes in the opposite direction, 
and by a pumping mechanism transporting substrates out of the organ. The differences 
Adult 
800 
PLASMA 
750 Newborn 
m 700 
= 
o 
ao 
UO 
> 
o 
SI 
Le) 
= 

minutes 
Fig. 4. Leucine transport from brain at different ages. Mice were injected with leucine at the be- 
. i - . S . - J . = . 
ginning of the experiments. (Newborn with 0.8 mg intraperitoneally, adults with 16 mg intra- 
venously and 16 mg intraperitoneally). 
in plasma to brain ratios at equilibrium indicate the variations in the efficiency of 
this transport from one substrate to another—or conversely, the ability of the tissue 
to take up various amounts of different substrates. It is difficult to establish at 
present that no transport of phenylalanine occurs from the brain; perbaps experi- 
mental circumstances can be varied in such a fashion that phenylalanine efflux 
against a concentration gradient can also be shown. 
The apparent lack of transport of phenylalanine out of the brain does not mean 
that no restriction to the uptake of this amino acid exists. After intravenous or 
intraperitoneal administration of phenylalanine, cerebral levels were below that of 
plasma, liver and muscle!’. 
Leucine transport against a concentration gradient could be shown in adult mice 
but not in newborn under similar circumstances (Fig. 4). The great number of 
changes in the brain during development makes it impossible to single out permeabil- 
ity changes among the many possible reasons! 24. One possible contributing factor 
to the greater uptake of substances in newborn also shown for glutamate®® and 
lysine”, could be a more fully developed transport out of the brain in the adult. 
References p. 563 
