AGENTS ON AMINO ACIDS IN MAMMALIAN BRAIN 507 
TABLE III 
ELEVATION OF GABA AND INHIBITION OF GABA-T BY AMINOOXYACETIC ACID* 


GABA-T 
Trial pede kes GABA umoles GA BA|g tissue/h 
No injection (mg %) Seay. oF ——— 
ies (h) pA No addn. + roo ug 
PyP/tube** 
I ) 30 41 37 
I 42 20 17 
3 78 19 16 
7 59 21 19 
2 oO 29 53 52 
39 25 24 
3 93 14 13 
7 66 27 20 
22 53 25 2 
49 39 3}5) 36 
69 34 31 30 
* Methods used for the assay of GABA and GABA-T are indicated in Table II. Two animals 
were used for each value of this table. The dose of aminooxyacetic acid (NH,OCH,COOH-!/, HCl) 
used was 50 mg/kg body wt., injected intraperitoneally. Fed Sprague Dawley females weighing 
200 + 20 g were used exclusively. 
** Pyridoxal phosphate was premixed with homogenates in Trial 2. The inhibition of GABA-T 
by aminooxyacetic acid was not reversed at any time period by in vitvo addition of PyP. 
no consistent inhibition of GAD was observed in the tissues of aminooxyacetic acid- 
treated rats. This is in sharp contrast to results obtained recently with GAD prepared 
from mouse brain acetone powders?!. In these 7m vitvo experiments, aminooxyacetic 
acid was shown to be one of the most potent inhibitors of GAD activity yet tested. 
Such results illustrate forcefully the subtle differences which may be observed in the 
effect of an agent 7m vitro and 7 vivo. 
Although changes in the level of an enzyme system have been demonstrated 77 
vivo, additional effects upon permeability and transport phenomena cannot be ex- 
cluded. Conversion to a substance other than the compound originally injected also 
is possible. Thus other considerations may be involved in explaining the differences 
in specificity of 7 vivo and 7m vitro inhibition with aminooxyacetic acid. 
The foregoing presentation has been used to illustrate the use of specific agents to 
change levels of free or loosely bound amino acids in animal tissues. This technique 
has and will continue to provide means to study the physiological significance of 
intrinsic amino acids in tissues and their biochemical and physiological interrelation- 
ship to each other and to other types of compounds. 
ACKNOWLEDGEMENTS 
This investigation was supported in part by Grants B-1615 and B-2655 from the 
National Institute of Neurological ‘Diseases and Blindness, National Institutes of 
Health, and a grant from the National Association for Mental Health. 
References p. 508 
