W. A. Fogel

Interference of aldehyde metabolizing enzymes with diamine oxidase/histaminase/activity as determined by 14C putrescine method.

Abstract The Δ 1 pyrroline formation, as an indicator of diamine oxidase activity according to Okuyama and Kobayashi 14 C putrescine test [1], has been investigated in several tissue homogenates. When guinea pig liver homogenate was used as a source of enzyme in the presence of aldehyde dehydrogenase inhibitors chloral hydrate and acetaldehyde the level of formation Δ 1 pyrroline was strongly increased in a dose-dependent manner. Also inhibition of aldehyde reductase by phenobarbital enhanced Δ 1 pyrroline formation, but to a lesser degree. In other tissues, with very high initial diamine oxidase activity (rat intestine, dog kidney) or with very low diamine oxidase activity (guinea pig skin, dog liver) the influence of these inhibitors was only slight. Pyrazole, an inhibitor of alcohol dehydrogenase exerted only a small effect on Δ 1 pyrroline formation. All aldehyde-metabolizing enzymes inhibitors, except pyrazole, were without effect on purified pea seedling and hog kidney diamine oxidases. The use of aldehyde-metabolizing enzymes inhibitors may help to reveal the real values of diamine oxidase activity, when tissues homogenates are used as a source of enzyme.

Histamine: Its metabolism and localization in mammary gland

1. Mammary gland of mouse (Mus musculus), rat (Rattus rattus), guinea pig (Cavia porcellus), cow (Bos taurus) and pig (Sus scrofa) contains different but always high concentrations of histamine. 2. Generally, the tissue histamine is localized in mast cells, although non-mast cell histamine immunoreactivity is also present in mammary glands of the mouse, cow and pig. No histamine immunoreactive nerves could be detected. 3. Mammary glands are able to synthesize and inactivate histamine; the activity of specific histidine decarboxylase and at least one of the catabolizing enzyme could be demonstrated. 4. Histamine fulfils basic criteria for being involved in physiological function of mammary glands.

The intracerebroventricularly administered mast cells degranulator compound 48/80 increases the pituitary-adrenocortical activity in rats

The effect of brain mast cells degranulation by compound 48/80 on the pituitary-adrenocortical activity, measured indirectly through corticosterone secretion, and the involvement of a histaminergic mechanism in that stimulation was investigated in conscious rats. All the drugs were given intracerebroventricularly (icv), histamine antagonists 15 min prior to compound 48/80. Compound 48/80 induced a significant dose- and time-related increase in the serum corticosterone levels. That increase, measured 1 h after adminstration of compound 48/80, was moderately diminished by icv pretreatment of rats with mepyramine and cimetidine, histamine H1- and H2-receptor antagonists. Three hours after administration of compound 48/80 mast cells of the thalamus and the hypothalamus were completely degranulated. At the same time the thalamus and the whole brain histamine levels were substantially higher than in the saline-treated control rats.The above results suggest that histamine liberated from the brain mast cells and central histamine receptors play a moderate role in increasing the pituitary-adrenocortical activity by compound 48/80.

Effect of Pargyline on Brain N‐tele‐Methylhistamine in Portocaval‐Shunted Rats: Relation to Amine Neurotransmitters

Abstract: HPLC determination of histamine, serotonin, dopamine, and noradrenaline in the brain tissue of rats with portocaval anastomoses (PCA) has revealed a selective increase in histamine concentration. In the posterior hypothalamus, the steady‐state level of the amine metabolites showed an inverse pattern; N‐tele‐methylhistamine(t‐MeHA), as estimated by gas chromatography‐mass spectrometry, was not changed significantly by portocaval shunting, whereas 5‐hydroxyindoleacetic acid (5‐HIAA) and homovanillic acid were more than doubled. Interestingly, the net increase in t‐MeHA concentration in response to pargyline (80 mg/kg i.p.) was almost the same for PCA and sham‐operated rats. This implies that the great enhancement of the histamine level in this area might be a consequence of the persistent stimulation of its synthesis and the unchanged activity of histaminergic neurons. In the rest of the brain, on the other hand, the steady‐state level of t‐MeHA was higher after PCA (3.8‐fold), as were the levels of 5‐HIAA and homovanillic acid. Surprisingly, t‐MeHA remained unchanged after monoamine oxidase blockade. Of the pargyline‐induced alterations in the concentrations of indoles and catechols, the most pronounced were those in the serotonin level; serotonin was elevated more than twofold in hypothalamus and more than 12‐fold in the rest of the brain, with a concomitant 80% decrease in 5‐HIAA. The dopamine and, to a much smaller extent, noradrenaline levels were also increased, and the levels of homovanillic acid and 3,4‐dihydroxyphenylacetic acid fell below the detection limit. The study suggests that at least two different mechanisms operate in the brains of PCA rats to counteract the excessive synthesis of neuromediators, e.g., increased deposition and increased metabolism.

Enzymatic histamine catabolism in vertebrate ontogenesis. A comparative study.

1. The synthesizing and degrading activities of histamine were determined in the liver and small intestine of developing guinea pig and chick embryos. 2. Though increasing with age, HDC values were always 2-3 orders of magnitude lower than those of degrading enzymes. 3. DAO activity on the other hand was 10-100 fold higher than HMT at all ages studied, suggesting a decisive role for oxidative deamination in control of tissue histamine levels. 4. Generally histamine levels were higher in tissues of developing guinea pig than chick embryo, however, in the laying hen intestine histamine concentration was approximately 5 times greater than in the adult guinea pig intestine.

A sum of14C-putrescine metabolites as a measure of DAO activity. Column chromatography assay

The rapid ion-exchange chromatographic method was developed for the separation of14C-putrescine from its metabolites arising from diamine oxidase (DAO, E.C. 1.4.3.6) catalysed reaction. The assay is linear for putrescine conversion. The assay is linear for putrescine conversion with both, time and enzyme concentration. With this method many samples could be analysed simultaneously.

Involvement of diamine oxidase in catabolism of14C-putrescine in micein vivo with special reference to the formation ofγ-aminobutyric acid

Tissues of mice killed 2.5 or 30 min after injection of14C-putrescine, contained14C-γ-aminobutyric acid, an unidentified14C-compound, and unchanged14C-putrescine. In mice pretreated with aminoguanidine, a powerful inhibitor of diamine oxidase, and then with14C-putrescine, tissue levels of the radioactive catabolites,γ-aminobutyric acid and the unidentified compound were markedly reduced. The data suggest that diamine oxidase is involved in the first step of putrescine metabolism and that intestine is the main site for this step. This and other aspects of putrescine metabolism are discussed.

Liver damage, voluntary alcohol intake and brain histamine

Liver dysfunction induced by portocaval anastomosis (PCA) in the rat is associated with a great reduction of hepatic alcohol and aldehyde dehydrogenase activities. Despite this, PCA rats voluntarily drank more alcohol than unoperated rats. When subjected to forced alcohol consumption, shunted rats maintained their exaggerated voluntary alcohol intake whereas unoperated rats developed aversion to alcohol. Hypothalamic levels of both histamine and histidine were very high in PCA rats. When these rats were chronically exposed to alcohol, there was a slight decrease in hypothalamic histidine concentration and consequently a lower histamine content. Chronic exposure to alcohol did not, however, influence hypothalamic tissue levels of histamine or histidine in unoperated rats. In both groups, chronic alcohol treatment exerted a stimulatory effect on hepatic alcohol metabolizing enzymes.

Histamine concentration and metabolism in mouse mammary gland during the estrous cycle.

Results and discussion The results are presented in Table 1. Among the parameters studied histidine decarboxylase and histamine concentration changed during the estrous cycle. They were at their highest during the estrus and their lowest in diestrus. In contrast, neither histamine N-methyltransferase nor transglutaminase activity varied significantly according to the hormonal status

Diamine oxidase (DAO) and female sex hormones

DAO activity in tissues of female guinea pigs was determined after the administration of estradiol or progesterone. Estradiol pretreatment elicited significant fall in DAO activity in the liver and specific increase in the uterus. The effect of progesterone was much less pronounced.