Abou, Yousif Z.

2018-01-31T11:16:07Z

2018-01-31T11:16:07Z

1968

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 histidine.

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 this view

http://hdl.handle.net/1842/26157

The University of Edinburgh

Annexe Thesis Digitisation Project 2017 Block 15

Study of the concentration of histamine in the hypothysis and brain of the rabbit and of the changes produced by treatment with amino acids and drugs

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy