G. Kahlson

MOBILIZATION AND FORMATION OF HISTAMINE IN THE GASTRIC MUCOSA AS RELATED TO ACID SECRETION.

The present work originated in two independent studies. First, it was decided to investigate the acid secretion in rats in which the histamine content of the gastric mucosa had been strongly reduced by subjecting the animals to inhibition of bistamine formation. It was known that semicarbazide injected in rats fed on a pyridoxine-deficient diet would very greatly diminish both the rate of formation and the content of histamine to a small fraction of normal in various tissues, particularly in the gastric mucosa (Kahlson & Rosengren, 1959; Kahlson, Rosengren & Thunberg, 1963). Under such inhibition it was found that the gastric mucosa secreted normally in response to injections of gastrin. At an early stage of the present work it thus appeared uncertain whether the histamine present in the mucosa was essential for the excitation of acid secretion. Concurrently experiments were done to investigate whether the phenomenon of increased mitotic index of certain gastric mucosal cells of rats on re-feeding, which was noted by Hunt (1957), would be accompanied by a corresponding increase in the level of histidine decarboxylase. This search was considered of interest since a correlation between cell renewal and level of histidine decarboxylase activity (Histamine-Forming Capacity, HFC), had been found in various tissues (for references see Kahlson, Rosengren & Steinhardt, 1963). In the course of this investigation it was found that re-feeding as well as injection of purified gastrin evoked an elevation of HFC of the parietal cell-carrying mucosa (corpus) to many times the fasting level. Even the small fraction of histidine decarboxylase activity persisting after inhibition of histamine formation was found to be similarly elevated by feeding or gastrin. With this latter discovery it was decided to confine the study mainly to experiments on the part played by mucosal HFC in inciting acid secretion. A preliminary communication of some of these observations has been given to the Physiological Society (Kahlson, Rosengren, Svahn & Thunberg, 1963).

The formation of histamine in the rat foetus

The foetus in the rat and man, the two species so far investigated, produces histamine at a high rate (Kahlson, Rosengren & Westling, 1958; KahLson, Rosengren, Westling & White, 1958; Kahlson, Rosengren & WVhite, 1959). This has been shown in the rat by (1) measurement of the urinary excretion of endogenous histamine, (2) study of the rate of urinary excretion of 14C-histamine after injections of 14C-histidine, (3) determination of the rate of histamine formation in foetal tissues in vitro, and (4) investigation of the effect ofremoving the foetus, without removing the placenta, on the excretion of histamine in the pregnant rat. The urinary excretion shows that in the rat the increase in histamine formation occurs at the 15th day of pregnancy and climbs to a peak in the last 1-2 days before term, when a precipitous fall in the rate of formation ensues. It would seem that the foetal formation of histamine during the last third of pregnancy is due to an increase in histidine decarboxylase activity, because the formation of the amine by foetal tissues in vitro is inhibited by semicarbazide and hydrazine in concentrations which are known to inhibit this enzyme. The rat foetus contains little histamine. Even at the peak of histidine decarboxylase activity and urinary histamine excretion (19th-20th day of gestation) the average concentration of histamine in the foetus is less than in the mother. It thus appears that foetal tissues produce the amine at a high rate, but bind histamine only loosely; and, since the histamine is in a state of rapid turnover, the amount found in the tissue is small. As the significance of the histamine production in the foetus is not known, it seemed desirable to identify the tissue(s) responsible for the high histamine-forming capacity. Further, to understand the discrepancy between histamine content and its rate of formation in the foetus, it appeared essential to study the binding of histamine in foetal tissues. A preliminary communication of these results has been given to the Physiological Society (Kahlson, Rosengren & White, 1959).

Accelerated mobilization and formation of histamine in the gastric mucosa evoked by vagal excitation

1. The changes in the rate of histamine formation and in the histamine content of the parietal cell containing region of the gastric mucosa have been studied in rats under the influence of agents which evoke or abolish vagal excitation.

Alterations in the activities of ornithine and histidine decarboxylases provoked by testosterone in mice

1 The urinary excretion of putrescine has been determined in female mice before and during repeated injections of testosterone. 2 Testosterone administration effected a striking increase in the excretion of free putrescine. 3 Ornithine decarboxylase (l‐ornithine carboxy‐lyase; E.C. 4.1.1.17) and histidine decarboxylase (l‐histidine carboxy‐lyase; E.C. 4.1.1.22) activities of mouse kidney and liver were examined. In the kidney, following testosterone administration, ornithine decarboxylase activity was found to be substantially elevated, whereas that of histidine decarboxylase was depressed. In the liver, by contrast, the activity levels of these enzymes were not significantly altered by testosterone treatment. 4 The possibility of a functional interrelation between putrescine and histamine, via the two enzyme activities investigated, is discussed.

Histamine formation in human wound tissue

Wund- und Granulationsgewebe bildet beim Menschen nach Hautschnitt in den ersten Tagen erhebliche Mengen von Histamin durch Dekarboxylierung von Histidin. Diese Fähigkeit zur gesteigerten Histaminbildung kann dabei nicht den Mastzellen zugeschrieben werden.

Histamine formation in bone marrow

Das Knochenmark der Ratte hat ein hohes Vermögen zur Histaminbildung durch Dekarboxylierung von Histidin.

Activities of decarboxylases of histidine and ornithine in young mice after injection of epidermal growth factor

Nachweis, dass der epidermale Wachstumsfaktor EGF, in 6–9 Tage alte Mäuse s.c. injiziert, eine 3 fache Steigerung der Histidin-Dacarboxylase-Aktivität in der Haut, nicht aber in anderen Geweben hervorruft, während EGF die Ornithin-Decarboxylase gar nicht beeinflusst.

Histamine formation in germinating seeds

Abstract In eleven plant species the germinating seeds have been examined for their histamine forming capacity, HFC. The spinach seedling exhibited a conspicuously high HFC which rose gradually as growth of the seedling proceeded. In the other species investigated, at every stage of germination, the HFC was much lower than in spinach. α-methylhistidine, a specific inhibitor of mammalian histadine decarboxylase, inhibited slightly but significantly the growth of spinach seedlings, whereas α-methylDOPA, a poor inhibitor of specific histidine decarboxylase, did not significantly inhibit the growth of the seedlings.

Retardation of protein synthesis in rat foetal liver on inhibiting rate of histamine formation.

1. The rate of protein synthesis, as gauged by the incorporation of [14C]leucine, has been determined in vitro in foetal and 5‐day‐old rat liver, tissues with respectively high and low histidine decarboxylase activity.