474 H. H. TALLAN 
able by paper chromatography". The amount of y-aminobutyric acid in a Factor I 
extract depends both on the time required for preparation and the length of storage!!6, 
McLENNAN!!® suggested earlier that the true active component of Factor I is a 
derivative of y-aminobutyric acid, from which the amino acid may be split during 
the preparation of the extract. There is evidence for the existence of an “occult” 
form of Factor I (refs. 62, 64; see also ref. 63), and the presence in brain extracts of 
a combined form of y-aminobutyric acid has been claimed*!, though the liberation of 
appreciable amounts of y-aminobutyric acid by hydrolysis of brain extracts has not 
been noted by other authors!, 16°. The presence of y-aminobutyrylhistidine has been 
shown" (see below), and some evidence for the presence of y-aminobutyrylcholine 
in dog brain has been presented!°4. MCLENNAN"! later used paper chromatography to 
separate Factor I into two fractions active on the crayfish stretch receptor. One frac- 
tion had chromatographic and pharmacological properties different from those of y- 
aminobutyric acid; the other fraction contained y-aminobutyric acid, but also a 
substance or substances with different pharmacological properties. More recently, 
McLENNAN"” has presented evidence that neither active fraction is ninhydrin-posi- 
tive ; he suggests that the activity is due to the same compound, as yet unindentified, 
present as a free cation in one fraction and as an uncharged complex in the other. 
Less y-aminobutyric acid is found in the brain of immature animals than in the 
brain of adults, and, with growth, there is a gradual increase to the adult levels; 
this has been shown with the mouse!43-145, rabbit22, chick embry oie: 235.45 ines 
tadpole, 145, and in man!27. Differences have not been noted, however, between 
calf embryo and ox brains!!. Besides its occurrence in the species listed in Table I, the 
compound is also present in alligator and opposum brain™®, and in crustacean nerve®®. 
Distribution studies show that gray matter contains twice as much y-amino- 
butyric acid as white matter!*. In human brain, the highest values reported are in 
caudate nucleus! 127 and cerebellum!®, but this is not in complete accord with 
results in other species. The concentration of y-aminobutyric acid in various parts 
of the rat'8. 1% 27, cat®1, 6, euinea-pig?®, and monkey®® brain has been determined. 
y-Aminobutyric acid occurs in spinal cord!*® (cf. ref. 68) at lower concentrations 
than in brain1%, but there seems to be little, if any, in peripheral nerves, though the 
compound does occur in retina®?» 1°, None was found in dog optic nerve and brachial 
plexus, 145, or in rabbit sciatic nerve!43; it is found in hen sciatic nerve, but not 
consistently*. Small amounts of Factor I activity are found in bovine oculomotor 
and trochlear nerves®’. A detailed study has been made of the distribution of Factor I 
activity in cattle brain®®; however, the values obtained cannot be equated with 
y-aminobutyric acid concentrations. 
b-Hydroxy-y-aminobutyric acid. This compound, which has much the same phar- 
macological actions as y-aminobutyric acid’, 144, has been proposed as the “true” 
chemical transmitter of inhibition in the mammalian brain?>. Much indirect evidence 
points to its presence in dog brain7>, 76, and its occurrence in rat7, human, cattle, 
mouse, and rabbit brain!?5 has been reported. Estimates of the amount present 
range from 0.5 wmole/g in rat brain?’ to 4.1 wmoles/g in cattle temporal lobe!®. 
However, the presence of the substance in mammalian brain has yet to be demon- 
strated unequivocally by isolation, and the use of isotopically labeled material has 
provided strong evidence against its presence. 
References p. 482/485 
