Inhibition of histamine catabolism suppresses fat intake but not the intake of carbohydrates and protein

Inflammation Research -     

Fasting duration influences the inhibition of food intake by histamine in chickens

This work was performed to investigate the effect of duration of fasting in the responses of chickens peripherally injected with histamine on the regulation of food intake. The animals were 16-week-old male chickens from layer-strain and the doses of histamine used were 500 and 1000 microg/kg of body weight. The non fasted chickens showed no effect of histamine on the food intake. When the animals were fasted during 4 h, injected with the histamine and immediately refed, the results showed a reduction of food intake only the first 15 min of the experiments with the dose of 1000 mug. In chickens fasted during 16 h or 26 h and refed, the histamine inhibited significantly the food intake at all time with the two doses. When the animals were fasted 16 h and refed during 60 min before the administration of the histamine, there is no inhibition of food intake. No effect on water intake has been registered in all the experiments. The blockade of the action of histamine injected in chickens fasted during 16 h by cimetidine and promethazine, show that the inhibition of food intake occurs through the H1 but not through H2 receptors. The fasting used in paradigm to investigate the effect of drugs such as histamine on the appetite, can affect differently the responses according to its duration, as observed here in chickens.     

Absorption and catabolism of histamine in sheep

1. The fate of dietary histamine in sheep has been studied. When 200 mg histamine diphosphate was administered into a rumen with normal contents the average time taken for the biological activity to disappear from the rumen was about 4 hr. In sheep starved for 60 hr the activity disappeared much more slowly.2. When 0.9% NaCl solution was substituted for the normal rumen contents and the rumen was isolated in situ under anaesthesia, the disappearance of histamine was scarcely detectable. About 1% of the radioactivity introduced into such rumen preparations as [(14)C]histamine was recovered in the urine during a 6 hr period.3. When both [(14)C]histamine and 200 mg unlabelled histamine diphosphate were administered into the rumen, between 4 and 15% of the radioactivity and 2 and 11% of the biological activity reached the duodenum.4. When jejunal loops isolated between two pairs of re-entrant cannulas were perfused with 0.9% NaCl solution containing histamine a considerable fraction of the histamine was absorbed from the loops.5. When [(14)C]histamine and 200 mg histamine diphosphate were administered into the rumen an average of 9% of the radioactivity appeared in the urine. When histamine was given into the abomasum the corresponding figure in a single experiment was 25%.6. Between 11 and 34% of the radioactivity administered into the rumen as [(14)C]histamine was exhaled as (14)CO(2). Most of the (14)CO(2) seemed to stem from metabolism of [(14)C]histamine in the ruminoreticulum whereas the contribution of the intestines to (14)CO(2) was very small.7. When [(3)H]histamine was administered into the rumen most of the radioactivity in the urine a few days after administration was in the form of tritiated water. The formation of (3)H(2)O is probably a result of histamine metabolism in the fore-stomach, analogous to the formation of (14)CO(2).     

Modulation of neuronal histamine in control of food intake

Neuronal histamine affects physiological functions of the hypothalamus. To investigate involvement of histamine receptors in feeding, histamine antagonists were infused into the rat third cerebroventricle. All H1- but no H2-antagonists tested, induced transient feeding during the early light when concentration of hypothalamic histamine was highest. No periprandial drinking was observed. Ambulation concomitantly increased during feeding. The effect on feeding was attenuated when brain histamine was normally low during the early dark or was decreased by alpha-fluoromethylhistidine (alpha-FMH). Bilateral microinjection indicated that the ventromedial hypothalamus, but not the lateral hypothalamus or the paraventricular nucleus, was a main locus for the induction of feeding by an H1-antagonist. The effect was completely abolished when brain histamine was decreased by pretreatment with alpha-FMH. Hypothalamic neuronal histamine suppresses food intake, at least in part, through H1-receptors in the VMH, and diurnal fluctuations of food intake may mirror neuronal histamine level.     

Transport, catabolism and release of histamine in the ruminal epithelium of sheep

Whereas intraruminal histamine does not affect healthy ruminants, histaminosis is apparent during ruminal acidosis. We therefore investigated the factors that, under physiological circumstances, prevent intoxication by intraruminal histamine and the disturbances occurring during acidotic or hypoxic epithelial damage. After mucosal (m) or serosal (s) application of 80 microM histamine, its flux across the isolated epithelia of the sheep rumen was determined radioactively (hist-rad flux) in Ussing chambers. The non-catabolized component of the hist-rad fluxes was determined by high-pressure liquid chromatography (HPLC) (histamine flux). The difference between hist-rad and histamine fluxes indicated efficient intraepithelial catabolism of histamine at pH 7.4 (m-s direction, 98.7%; s-m direction, 93.3%). Both 0.1 mM 2,4-dinitrophenol (DNP) and mucosal acidification to pH 5.1 increased hist-rad fluxes and decreased catabolic efficiency. pH-dependent secretion of histamine was indicated by differences between m-s and s-m fluxes of histamine and/or hist-rad. Epithelial permeability to hist-rad and mannitol was similar and their fluxes correlated partly. Epithelial release of endogenous histamine was 1.5 pmol x cm(-2) x h(-1) and was not increased by the mast cell stimulator, compound 48/80 (10 ng x ml(-1)). We conclude that histamine absorption across the intact epithelium is efficiently restricted by a low permeability to histamine in combination with catabolic and secretory processes. Especially increases in paracellular permeability and/or inhibition of catabolism enhance histamine absorption.     

Paracellular tightness and catabolism restrict histamine permeation in the proximal colon of pigs

Luminal histamine concentrations can be very high in the intestine without eliciting clinical histaminosis. The intestinal mechanisms that possibly prevent systemic intoxication by luminal histamine were investigated in the present study. Porcine colonic epithelia were mounted in Ussing chambers. After unilateral application of partially (3)H-labelled histamine, mucosal-to-serosal (MS) and serosal-to-mucosal (SM) flux rates were calculated from the contralateral appearance of histamine and the radioactive histamine label (hist-rad; representing histamine plus catabolites). A discrepancy between histamine and hist-rad fluxes was observed in both flux directions, indicating efficient histamine catabolism at all histamine concentrations tested (5, 50 and 100 microM). Catabolism exceeded 65% at 100 microM histamine and reached approximately 100% at 5 microM histamine. Blockade of histamine N-methyltransferase by amodiaquin (100 microM) abolished catabolism completely, whereas blockade of diamine oxidase by aminoguanidine (100 microM) was less effective. MS fluxes of histamine and hist-rad correlated with mannitol fluxes. Mast cell stimulation with the calcium ionophore A23187 (1 microM) induced a twofold larger histamine appearance on the serosal side than the mucosal application of 100 microM histamine. It is concluded that histamine permeation across the porcine proximal colon is restricted by low permeability and sequential catabolism by histamine N-methyltransferase and diamine oxidase.     

Ketotifen-induced histamine release,inhibition of histamine secretion and modulation of immune response

In concentrations above 0.1 mM Ketotifen (KT) induced secretion of histamine from rat and mouse mast cells, but not from human basophils. In the same concentrations KT inhibited histamine release from rat mast cells, induced by compound 48/80 and histamine release from basophils, induced by anti-IgE-antibodies and concanavalin A. At low concen-tration (0.05–0.005 mM) KT enhancedin vitro phytohemagglutininin-induced proliferative response of human lymphocytes. The immunostimulating effect of KT was confirmedin vivo. In doses 0.18–1.4 g/mouse KT significantly increased the number of antibody-producing cells (APC) in spleens of mice immunized by sheep red blood cells (SRBC). KT stimulated both IgM- and IgG-immune response to SRBC.     

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.     

Changes in histamine synthesis,tissue content and catabolism in human breast cancer

The present study in 10 breast cancer patients supports the concept that newly synthetized, nascent histamine is involved in tumour growth. Histidine decarboxylase (HDC) activity is increased in mammary tumour tissue compared to healthy mammary gland-, skin- and muscle tissue in all but one patient studied. The newly formed histamine is probably not stored in the tumor tissue. Significantly decreased histamine concentrations were measured in parallel samples in the tumour tissue. Moreover, the preliminary results from urinary analysis of histamine and N-methylhistamine in 3 of the 10 patients studied showed a significant decline after tumour extirpation compared to preoperative values.This study is part of a joint project between the University of Malaga and the Phillips-University of Marburg. The project is supported with a grant from the CAICYT (spain) (PA-85-0371).     

Intestinal monoamine oxidase: Does it have a role in histamine catabolism?

The importance of intestinal diamine oxidase in histamine catabolism was proved in several series of experiments. However, intestinal monoamine oxidase might also be involved in histamine degradation either by direct deamination or by the deamination of methylated products. The soluble fraction of intestinal monoamine oxidase was purified and tested for its properties and substrate specificity by three different methods which are described in detail. Using 0.15M phosphate buffer the optimum pH was 7.4–7.6. TheK _m values for serotonin and tyramine were 0.2 and 0.3×10^–3 M. The most favoured substrates of the enzyme were tyramine, tryptamine and serotonin, but it was not pissible to classify the enzyme as a type A or B monoamine oxidase only by its substrate specificity. Histamine and ring methylated derivatives were not attacked by intestinal monoamine oxidase. This means that in the intestinal mucosa the oxidative pathway of histamine is completely catalysed by diamine oxidase.Supported by a grant from the Deutsche Forschungsgemeinschaft (Ku 464/1).Supported by a grant from the Deutsche Forschungsgemeinschaft (Lo 199/7).     

The inhibition of histamine release by antiallergic drugs.

Three new antiallergic drugs, Doxantrazole, PRD-92 and N5', as well as disodium cromoglycate, inhibited the IgE-mediated PCA reaction in the rat triggered by the homologous antigen, but did not have an antagonistic effect on histamine itself. Moreover, all the drugs examined caused in vitro inhibition of antigen-mediated histamine release from peritoneal mast cells and chopped lung tissue of sensitized rats producing IgE antibodies. Doxantrazole had a synergistic effect on the inhibition of histamine release by isoproterenol, whereas the other drugs were devoid of this capacity. PRD-92 and N5' inhibited the ionophore A23,187 induced histamine release, but did not have any effect on the D2O-enhanced histamine release which was triggered by antigen.     

Glucocorticoid inhibition of antigen-evoked histamine release from human skin

Prednisolone causes a dose-related inhibition of antigen-evoked histamine release from IgE-sensitized human skin in vitro. The effective concentrations are of the same order as are achieved in plasma therapeutically.

Analysis of prednisolone inhibition shows that it acts on the second histamine release stage, antigen—antibody combination being unaffected.

In contrast with the traditional view, our results show that, at least in human skin, glucocorticoids can inhibit antigen-evoked histamine release.