The distribution and fate of radioactive histamine in the rat

Abstract

It is universally accepted that histamine, whether of endogenous or exogenous origin, is disposed of by the two processes of enzymic destruction and of excretion through the renal tract. There is, however, little information about the way in which exogenous histamine is brought into contact with its specific enzymes. The rapid clearance of histamine from the blood after its intravenous injection (Rose & Browne, 1938) suggests that the uptake of histamine by the tissues may be a method for its immediate disposal from the blood, related to, and as important as, its subsequent metabolic destruction and renal excretion. The details and mechanism.s of this process are still unexplained. The purpose of the present experiments was to investigate this process by means of radioactive histamine, and to examine the fate, distribution and transfer through the tisues of exogenous histamine introduced into the circulation of the living orgamsm. Rose & Browne (1938) suggested that a powerful mechanism existed for the uptake of histamine into the tissues from the circulating blood of the rat, but their results have been criticized on account of the large doses of histamine which they used. Such doses may cause disturbances in the circulation after intravenous injection. In the present experiments, therefore, a relatively small dose of histamine was used for injections so that effects due to circulatory changes could be excluded. METHODSAlbino male rats of the Wistar strain weighing 125-150 g were used in all the experiments. After the intravenous injection of radioactive histamine, blood was removed at intervals of 15, 20 and 40 sec through a fine cannula inserted into the carotid artery, and at intervals from 1 to 240 min

The continuous bioassay of the release and disappearance of histamine in the circulation

“…These results are compatible with the 50% disappearance of histamine during one circulation (15-20 s) in all vascular beds of the dog (Table 1, Figure 3). Halpern et al (1959) also found that more than 50% of circulating histamine disappears within 30 s in the rat. This rapid disappearance of histamine from the circulation must be due to its removal or inactivation by tissues (Rose & Brown, 1938;Emmelin, 1951) and, as indicated in this paper, does not depend on blood pressure.…”

“…The bulk of the histamine taken up by tissues is catabolized in situ. However, some tissues may release it back to the circulation when it will be metabolized by other tissues or excreted by the kidneys (Emmelin, 1951;Halpern et al, 1959;Green, 1967).…”

Uptake, disposition and metabolism of histamine in isolated heart preparations

“…On the other hand, all organs which have been examined, including the heart, take up histamine (Mannaioni, 1972). The first evidence of cardiac histamine uptake was given by Halpern, Newen & Wilson (1959) showing that after intravenous injection into rats the largest concentrations of the amine were found in the heart, lung, liver and kidney, mostly reflecting tissue blood flow. Further insight into the uptake of histamine by hearts of different animal species was afforded by in vivo studies on the fate of labelled histamine after intravenous infusion into the mouse and rat (Snyder, Axelrod & Bauer, 1964; Reilly & Schayer, 1970;1971), cat (Johnson, Beaven, Erjavec & Brodie, 1966) and dog (Ryan & Brody, 1970).…”

Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice

“…Nonetheless, a considerable amount of histamine is still excreted unmodified (35,37), and in humans, cases of histamine intolerance due to ingestion of spoiled fish (40) or other amine-rich foods (41), endogenous histamine overproduction, or an imbalance between the accumulation of histamine and its elimination are known to result in elevated plasma histamine levels and severe allergic reactions (41) or recurrent anaphylaxis (42). This suggests that histamine exceeds its physiological usefulness during exposure to large amounts of it, and this overwhelms the inactivation mechanisms, causing unwanted effects on blood pressure, vascular tone, and permeability.…”