The rise of brain histamine seen after the
infusion of histidine was probably due to local
decarboxylation of the amino acid* Other factors
however, may have contributed to the result and
are discussed below:
(a) Histamine in whole blood. Histidine
may have been decarboxylated in formed elements
of blood, particularly platelets (S. 1/5), thereby
leading to a rise of histamine in whole blood.
Residual blood in the cerebral vessels would then
increase the concentration of histamine extractable
from brain. This assumption was tested in various
ways and the following evidence was obtained:
(1) An increase in whole blood histamine
after treatment with histidine was not detected
(Table 18 and Pig. 6). Had there been an increase
one might have expected to find a uniform concentration of the amine in various parts of the
brain. But this was not sot the rise occurred
unevenly and corresponded to the pattern of distribution for histamine.
(2) In 6 rabbits out of 9, infused with
histidine ( 3 x 500 mg/Kg over 24 hr), the head
was perfused with Ringer-Locke solution (S. 2/6).
The concentration of histamine in brain was not
diminished and the rise was comparable with that
obtained after bleeding only (Table 18).
(b) Histamine in Decarboxylation
of histidine by platelets and other tissues of
the body may have raised the plasma histamine.
However, when histamine was infused intravenously
the concentration in the hypothalamus and thalamus
did not rise significantly (Table 19 and Pig. 7).
The results of all these experiments support
the conclusion that most of the histamine extract-'
able from brain of histidine-treated rabbits is
histamine of tissue origin and not derived from
residual blood or formed as an artifact from
Although the uptake of histidine by brain
has been studied in other species both in vitro
(Neame, 1961, 1962) and in vivo (Kamin and Handler
1951), similar studies have yet to be performed
in the rabbit. In the present work (Appendix 1 )
a high concentration of histidine in the rabbit
brain was found after treatment with the amino
acid. Since histamine disappears rapidly from
the circulation (S. 1/9) and does not enter the
brain in measurable quantities (S. 1/8, Table 19
and Fig. 7), it may be concluded that the rise
of histamine concentration occurred because histidine entered the brain and was decarboxylated.
Hlstidine, DOPA and
5-HTP are deearboxylated in the cytoplasm (see
Gaddum, 1956; Rosengren, I960), During the
shuttling between the cytoplasm and granules,
histamine runs the risk of methylation (S. l/7).
The final concentration of histamine in cells may
therefore represent the amine which has escaped
catabolism (Green, 1962). "The likelihood of
a highly organized system in the synthesis and
intracellular transport of the amines is strengthened by observations suggesting that the cell may
handle exogenous and endogenous amines differently
(Green, 1962)§ intact brain formed more MH from
exogenous histamine than from endogenous histamine
(White, I960), The same cells that contain biogenic amines almost invariably contain enzymes
that catabollze them. The activity of these
enzymes is so high that the persistence of
significant stores of amines would be most improbable unless the enzymes were either inactive In
situ or not accessible to the amine.
The massive increase in brain histamine,
which followed the infusion of histidine, was not
accompanied by obvious pharmacological effects on
behaviour this might suggest that the amine
was stored in granules. The slow disappearance
of the newly-formed histamine (Fig. 8) supports