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PubMed1979

Effect of solvent on the histamine-releasing, enzyme-releasing, and mitogenic properties of the calcium ionophore A23187.

The potency of the calcium ionophore A23187 in inducing three activities of human leukocytes (histamine secretion from basophils, enzyme secretion from PMNs, and proliferation of lymphocytes) was markedly dependent on the solvent (DMSO versus ethanol versus aqueous buffer) used for its initial sonication. While 0.1 micrograms/ml of DMSO- and ethanol-solubilized A23187 induced maximal histamine release from basophils and histaminase release from PMNs, concentrations of aqueous buffer-sonicated ionophore of greater than or equal to 1 microgram/ml were required for an equivalent response. Ionophore sonicated in organic solvents caused a maximum release of 40% of PMN beta-glucuronidase, at an optimal concentration tenfold higher than that required for maximal histaminase release; ionophore sonicated in aqueous buffers, even at high concentrations, effected a release of less than 5% of cellular beta-glucuronidase. A23187 also induced lymphocyte proliferation over a narrow concentration range; 0.05 micrograms/l of DMSO-sonicated ionophore induced optimal proliferation and concentrations greater than or equal to 0.2 micrograms/ml were toxic. Twofold higher concentrations of ethanol-sonicated ionophore and fourfold higher concentrations of aqueous-sonicated ionophore were necessary for maximal proliferation, and the magnitude of the maximal response with aqueous-sonicated A23187 was only one-half that of DMSO-solubilized agent. Ionophore-induced release of histamine from basophils and enzymes from PMNs was not cytotoxic, since ionophore induced neither LDH nor histamine release from heat-treated (47 degrees C) cells. These results explain several previous, discordant reports on the presence or absence of an effect of A23187 on cellular secretory events, on differing dose-response relationships, and on cytotoxic versus noncytotoxic mechanisms of action.

Anti-Bacterial Agents↗
PubMedDate not supplied

Early increase in histamine concentration in the islets of Langerhans isolated from rats made diabetic with streptozotocin.

Sprague-Dawley rats were separated in 4 groups. G1 received streptozotocin (ST). G2 received nicotinamide (NC) followed by ST. G3 was a NC control and G4 was a citrate control. The rats were sacrificed after 28 h and the islets isolated. Histamine and histaminase were determined. In the islets there was an increase in histamine content in G1 and a smaller increase in G2. The first two groups differ significantly and also in relation to the control groups. A decrease in islet histaminase does not seem responsible for the increased histamine, since group 2 (NC + ST) which had no diabetes, had a lower activity than group 1 (ST). It is suggested that histamine liberation by ST may be related to the diabetogenic effect of this drug.

Amine Oxidase (Copper-Containing)↗
PubMed1992

Further studies on semicarbazide-sensitive amine oxidase activities (SSAO) of white adipose tissue.

1. White adipose tissue (WAT) from mice, rabbits, pigs and human subjects was investigated for the characterization of the tissue-bound semicarbazide-sensitive benzylamine oxidase activities (SSAO) present in each species. 2. Enzymes from mice, rabbits and pigs shared similar biochemical characteristics: they exerted histaminase activity, oxidized methylamine and acetylputrescine and were completely blocked by carbonyl reagents and by 3,5-ethoxy-4-aminomethylpyridyne (B24), in a dose-dependent fashion. 3. SSAO activity from human WAT had a lower affinity for benzylamine compared with enzymes in the other species and did not show any histaminase activity. 4. These results show that SSAO from human tissues might have different properties from SSAO of other species.

Adipose Tissue↗
PubMedDate not supplied

Serotonin metabolism and platelet monoamine oxidase activity in patients with medullary carcinoma of the thyroid and pheochromocytoma.

Occasional patients with medullary carcinoma of the thyroid (Multiple Endocrine Neoplasia Type II [MEN II]) are reported to have excessive serotonin (5-HT) production from the MCT; almost all patients with metastatic MCT have elevations in plasma concentration of the amine oxidase, histaminase. The elevated 5-HT production is thought ot contribute to the troublesome diarrhea experienced by patients with MEN II. We compared the urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the principle metabolite of 5-HT, of 33 patients with MCT with the urinary excretion of 5-HIAA in 33 control subjects. Six of the 33 MCT patients (18%) had severe diarrhea. The 5-HIAA excretion of the MCT patients did not differ from that of normal subjects. We also compared the platelet monoamine oxidase (MAO) activity of 27 MCT patients and 27 control subjects. The platelet MAO activity of the two groups did not differ. The 5-HT content and MAO activity of 6 of the MCTs was similar to normal thyroid tissue. The MAO activity of two follicular adenomas of the thyroid was greater than the MAO activity of MCTs. In contrast to the uniform elevation of plasma histaminase in patients with MCT, the platelet MAO activity is not altered and the majority of MCTs do not produce excessive amounts of 5-HT.

Adolescent↗
PubMed1993

Histamine content, synthesis and degradation in nasal mucosa and lung of guinea-pigs treated with toluene diisocyanate (TDI).

We have reported the presence of a histamine synthesizing enzyme, histidine decarboxylase (HDC), and histamine degrading enzymes, histamine N-methyltransferase (HMT) and histaminase (diamine oxidase, DAO) in human nasal mucosa and the histamine content of the mucosa. In this study, we demonstrate the influences of the toluene diisocyanate (TDI) treatment on the histamine content and these enzyme activities in guinea-pigs as an animal model of respiratory hypersensitivity. Application of TDI to the nasal vestibuli induced intense nasal allergy-like and mild asthma-like responses in TDI-sensitized guinea pigs. Increases in the histamine content and HDC and HMT activities were observed in the nasal mucosa and lung of TDI-sensitized guinea pigs. No apparent changes in the histaminase activities were observed in either the nasal mucosa or the lung. These data suggest that the turnover rate of histamine is increased in the nasal mucosa and the lung of guinea pigs with respiratory hypersensitivity.

Amine Oxidase (Copper-Containing)↗
PubMed1981

Endocrine-related biochemistry in the spectrum of human lung carcinoma.

The association of hormonal syndrome and APUD (amine precursor uptake, decarboxylase) features with small cell carcinoma of the lung (SCC) has suggested that SCC has a separate cell origin from other major forms of lung cancer. Recently, however, both SCC and non-SCC lung cancers have been found to contain small polypeptide hormones and APUD enzymes. The present study quantitates, in 50 samples of human lung cancer tissue, relationships among the 4 major types of lung cancer and endocrine-related properties. Among 4 parameters measured (dopa decarboxylase, histaminase, beta-endorphin, and calcitonin), no single marker clearly separated SCC from non-SCC lung cancer. The high activity of dopa decarboxylase (the "D" in "APUD") best separated SCC from non-SCC, but significant overlap existed even for this critical APUD property. In fact, 2 adenocarcinomas had among the highest concentrations of dopa decarboxylase, histaminase, and calcitonin of any tumor tissue studied. The simultaneous appearance of high levels of 2 or more markers favored SCC. This was quantitated by deriving an index unit based upon the product of the values for the 4 markers in each lesion. This index separated all SCC from all non-SCC lung carcinomas, with the exception of the above 2 adenocarcinomas. Endocrine-related properties thus occur throughout the spectrum of human lung cancer. Biochemical differences between the major histopathological types are quantitative rather than qualitative and probably reflect the fact that the major forms of lung cancer represent a continuum of differentiation within a common cell lineage which includes both SCC and non-SCC lung tumors.

APUD Cells↗
PubMed2005

An outbreak of histamine poisoning after ingestion of the ground saury paste in eight patients taking isoniazid in tuberculous ward.

OBJECTIVE: To determine the cause of outbreak mimicking food poisoning, we studied the toxic polyamine contents of the food and analyzed the clinical characteristics of the affected eight patients. PATIENTS AND METHODS: Eight cases of histamine poisoning which occurred in tuberculous patients after dinner in our hospital were analyzed by clinical and biochemical methods. We examined the contents of four representative toxic polyamines, histamine, putrescine, cadaverine and tyramine, of the each food of the dinner and their serum concentrations of the monoamine oxidase (MAO), one of histaminases, using radioimmunoassay. RESULTS: The allergy-like symptoms such as flushing, headache, palpitation, itching, wheezing, dyspnea and diarrhea appeared from 20 minutes to two hours after ingestion in those eight patients taking isoniazid (INH), although the other 378 inpatients had no symptom. The histamine content of the ground saury paste was increased to 32 mg/100 g of food, however, the toxic level of food poisoning is less than 50 mg/100 g of food. All eight patients were taking INH, and their serum concentrations of MAO were decreased. CONCLUSION: We concluded that this accident was the histamine fish poisoning. We speculated that those allergy-like symptoms were due to both the increased histamine in the food made with the saury under poor storage conditions and the patients' reduced histaminase activities due to INH. We should perceive possible adverse effects depending on the interactions between certain drugs and food.

Adult↗
PubMed1989

The close relationship of heparin and the vessel wall.

For over 100 years heparin has attracted interest because of its anticoagulant powers. Commercial heparin has now been shown to be a mixture of over 100 different closely related sulfated polysaccharides of which only 10% activate antithrombin-III. Fifty years ago the original research teams in Toronto and Stockholm in demonstrating the clinical uses of heparin observed that antithrombotic activity did not correspond to levels of anticoagulation. It has been shown that: (a) Heparin accumulates rapidly and specifically in the endothelium against a concentration gradient of hundreds- to thousands-fold. (b) Experimental thrombosis, however produced, is accompanied by a marked decrease in the electronegative charge of the vessel wall and the charge is restored in all cases by heparin. (c) The normal electronegative charge is due to glycosaminoglycans. Heparin possesses the strongest electronegative charge of these substances and is present in the vessel wall as a component of a larger heparitin (sulfate) proteoglycan molecule. (d) Maintenance of the normal electronegative charge depends on adequate supply of oxygen (adequate blood flow). (e) Commercial heparin releases enzymes from the endothelium, lipoprotein lipase and histaminase (D.A.O.). Lipoprotein lipase changes the composition of plasma lipids and lipoproteins and histaminase provides a check for fat absorption. The release of these enzymes decrease and prevent atherosclerotic changes. (f) After administration of commercial heparin, heparin isolated from the plasma has higher antithrombin activity than that injected. The heparin taken up by the endothelium is returned with greater activity. The anticoagulant effect of administered heparin does not produce hemorrhage since this requires simultaneous occurrence of defects in the vascular factor of hemostasis (the result of stress or pituitary-adrenal imbalance) or platelet defect. Thus, clinical effectiveness of heparin is an expression of its close relationship to the vessel wall.

Animals↗
PubMed1988

Histamine and ascorbic acid: a survey of women in labor at term and significantly before term.

In ascorbic acid-requiring species (human, guinea pig), elevations of circulating histamine occur as the result of marginal ascorbic acid status. Marginal ascorbic acid status during pregnancy is associated with preeclampsia, abruption, and prematurity. Furthermore, circulating histamine is known to be elevated in these complications perhaps as a result of placental dysfunction which diminishes normal placental histaminase. We hypothesized that women with preeclampsia and premature labor would have elevated histamine and the lowest concentrations of ascorbic acid. Plasma total whole blood histamine and ascorbic acid were surveyed in women in term (T) and preterm (PT) labor. Blood histamine was elevated in PT compared to T labor but so was plasma ascorbate, indicating that marginal ascorbate status does not cause the elevated circulating histamine observed in PT. However, marginal ascorbate status concomitant with reduced placental histaminase may contribute to further increases in circulating histamine and to any pathology which might result from elevated histamine. Regression analysis of histamine on ascorbate for T and PT labor revealed a significant inverse relationship between ascorbate and histamine only in PT labor (p less than 0.027). An unexpected finding was that a history of maternal cigarette smoking, to a degree which resulted in marginal ascorbic acid status, confounded the relationship between ascorbate and circulating histamine in T labor.

Adult↗
PubMedDate not supplied

[Change in biogenic amine metabolism in botulin poisoning].

An increase in content of serotonin, histamine, the elevated histaminase activity in tissues and an increase in excretion of 5-hydroxyindolylacetic acid with urine were observed in experimental botulism, accompanied by paresis of sceletal muscles. As the paralysis progressed content of histamine gradually decreased in nervous tissue but it remained to be increased in the internal tissues although the histaminase activity was high. At the same time, content of serotonin was maintained at an increased level in the nervous tissue, but it was normalized in several internal organs. Excretion of 5-hydroxyindolylacetic acid with urine was decreased. LD50 of botulinic toxin was titrated in mice, which were simultaneously administered with preparations increasing or decreasing the synthesis and the activity of biogenic amines. The data obtained suggest that the impairments in metabolism of biogenic amines could be important for development of the intoxication.

Amine Oxidase (Copper-Containing)↗
PubMed2003

Induction and characterization of a novel amine oxidase from the yeast Kluyveromyces marxianus.

An amine oxidase from the yeast Kluyveromyces marxianus was induced, purified and completely characterized; it was shown to belong to the class of copper-containing amine oxidases (E.C. 1.4.3.6). The enzyme was induced by putrescine and, very strongly, by copper(II); structural-functional characterization of the enzyme was performed, including determination of molecular weight, glycosylation, copper and TPQ content, isoelectric point, K(M) and k(CAT) (with benzylamine as substrate), pH, temperature and ionic strength effect on catalysis, substrate and inhibitor specificity. A 700 bp clone was isolated containing the cDNA that encodes for the C-terminus of the enzyme; the amino acid sequence deduced (the first available for a benzylamine oxidase from yeast) was compared to that of other copper amine oxidases from microorganisms and higher organisms. From the results obtained, the putrescine/benzylamine oxidase from Kluyveromyces marxianus was found to have a good homology with other enzymes of this class from microorganisms, and particularly with AO I from Aspergillus niger. Nonetheless, some features resulted closer to those of animal amine oxidases and histaminases. Some potential biotechnological applications are proposed. The cDNA Accession No. is AJ320485.

Amine Oxidase (Copper-Containing)↗
PubMed1998

Semicarbazide-sensitive amine oxidase activity in the human heart.

A semicarbazide-sensitive amine oxidase with affinity for benzylamine (Bz.SSAO) was found in the human heart. This enzymatic activity has a K(m) of 278 +/- 35.3 microM and a V(m) of 114.7 +/- 14.7 nmol mg-1 min-1 (mean +/- SE of eight hearts) for benzylamine and is strongly inhibited by 1 mM histamine and by B24, a specific inhibitor of Bz.SSAO. No diamine oxidase activity was found in the human heart. The levels of MAo and B were assayed: MAO A showed a K(m) of 137.1 +/- 16.2 microM and a V(m) of 10.4 +/- 2.5 nmol mg-1 min-1 for serotonin; MAo B had a K(m) of 9.9 +/- 1.6 microM and V(m) of 4.3 +/- 1.1 nmol mg-1 min-1 for beta-phenylethylamine (mean +/- SE of seven hearts). The human heart has high MAO B activity and Bz.SSAO with histaminase activity.

Adult↗
PubMed1976

Influence of pregnancy on the development of various gastric lesions in rats.

The influence of pregnancy, and to some extent lactation, on various gastric lesions in rats were studied. Shay ulceration and gastric lesions induced by cold-restraint stress and ulcerogenic agents, such as acetylsalicylic acid (ASA), reserpine, or epinephrine, in rats were significantly aggravated by pregnancy (day 20 of pregnancy). Gastric hypersecretion, which was observed during pregnancy in pylorus ligation preparation, appears to contribute to the mechanism of aggravation of gastric lesions. ASA induced a marked back-diffusion of acid in pregnant rats which might resulted in the aggravation of ASA-induced gastric lesions. In contrast, histamine-induced gastric lesions were markedly inhibited according according to the progress of pregnancy but after 10 days' lactation returned to the level seen in nonpregnant rats. The histaminase inhibitor aminoguanidine strongly aggravated the histamine-induced gastric lesions in pregnant rats as compared with the non-pregnant ones.

Animals↗
PubMed1983

Diamine oxidase in the hen.

In adult hens diamine oxidase (histaminase) activity was found in gastrointestinal tract (with the highest value in ileum), liver and spleen. Intestinal diamine oxidase is predominantly a particle-bound enzyme. In the intestine oxidation of putrescine leads to delta 1-pyrroline formation, in liver both delta 1-pyrroline and gamma-aminobutyric acid are formed. The inhibitor properties of hen intestinal and rat intestinal diamine oxidases are very similar and differ from pea seedling diamine oxidase. The natural dipeptides carnosine and anserine are relatively potent inhibitors of hen intestinal diamine oxidase.

Amine Oxidase (Copper-Containing)↗
PubMed1981

Putrescine metabolism and the study of diamine oxidase activity in vivo.

The catabolism of 14C-putrescine (1,4-tetramethylene-diamine) to labeled CO2 in small laboratory animals has been studied extensively in order to establish the influence of nutritional, endocrine and other factors on this process. Special attention has been paid to treatments that are known to affect the activity of diamine oxidase (DAO, histaminase, EC, 1.4.3.6), a copper-containing enzyme characteristically inhibited by semicarbazide. Thus, copper-deficient rats metabolize putrescine more slowly than their controls. Antimalarial drugs that inhibit histamine N-methyltransferase also inhibit putrescine catabolism in vivo and DAO activity in vitro. Adrenalectomized rats metabolize the diamine at a reduced rate, a result consistent with the previously demonstrated decrease of DAO in the tissues of several species of animal. There is no effect on the rate of catabolism of putrescine when thyroid state is altered. Heparin (up to 15,000 U/kg), which releases DAO from the small (0.1 mg/kg), intestine, and aminoguanidine (0.1 mg/kg), which inhibits the enzyme powerfully, both cause decreased rates of catabolism of the diamine in rats. The putrescine-catabolizing ability returns with a half-time of recovery of 15-18 h, corresponding to the estimates of SHAFF and BEAVEN [36] for recovery of intestinal DAO activity following administration of heparin or cycloheximide. Together with out other results this suggests that what is being measured by putrescine catabolism depends to a significant extent on the activity of DAO in vitro.

Amine Oxidase (Copper-Containing)↗
PubMed2004

Regulation of Con A-dependent cytokine production from CD4+ and CD8+ T lymphocytes by autosecretion of histamine.

OBJECTIVES: Previously we have shown that both CD4+ T cells and CD8+ T cells produce histamine when activated with Con A. The aim of this study was to examine whether cytokine production by these cells is regulated by autosecretion of histamine. MATERIALS: CD4+ and CD8+ T cells were separated from spleen cells of C57BL/6 mice and mice lacking the H1 receptor (H1R) or H2R, using anti-CD4+- and anti-CD8+-coupled magnetic beads, respectively. RESULTS: Depletion of the H1R resulted in decreases in the release of IL-2 and IL-10 from both CD4+ and CD8+ cells and increases in the release of IL-4 from CD4+ T cells and IFN-gamma from CD8+ cells. Mice lacking the H2R showed up-regulation of IFN-gamma secretion from CD8+ cells and of IL-4 from CD4+ and CD8+ T cells. Release of IL-2 and IL-10 from CD4+ as well as CD8+ cells was down-regulated in these mice. Both CD4+ and CD8+ T cell fractions synthesized histamine, which was enhanced in the H1R-deficient CD8+ T cells. Treatment of the cells with alpha-fluoromethyl-histidine, a specific inhibitor of HDC, or histaminase increased IFN-gamma from CD8+ cells, whereas it had no appreciable effect on IL-4 secretion from CD4+ cells. CONCLUSION: These results suggest that cytokine production by CD4+ and CD8+ T lymphocytes is regulated by autosecretion of histamine.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Histamine synthesis and catabolism in various tissues in diabetic rats.

In view of the observations that (1) plasma histamine concentrations are significantly higher in diabetic patients and diabetic rats than those in controls, and (2) tissue concentrations of histamine are elevated in rats with experimental diabetes, we have investigated histamine synthesis, as reflected by histidine decarboxylase (HDC) activity, and histamine catabolism, as reflected by histaminase activity, in various tissues of the diabetic rat. Rats with streptozotocin-induced diabetes mellitus (DM) showed an increase in histamine synthesis in various tissues; this was most marked in the aorta and to a lesser, but significant, extent in the kidneys, lungs, and heart, but not in the brain, stomach, or skin. Tissue content of histamine was significantly increased in all tissues except the stomach and skin. We conclude that tissue histamine synthesis is significantly increased in diabetic animals and that this increase is most marked in the aorta. The elevation in HDC activity in these tissues probably accounts for the increase in tissue and plasma concentrations of histamine in diabetic animals, since there is no change in histamine catabolism. This increase in histamine synthesis and release may contribute to the pathogenesis of endothelial damage in diabetic microangiopathy and macroangiopathy.

Animals↗
PubMed1977

Adverse reactions to isoniazid on ingestion of fish with a high histamine content.

On eating preparations of a particular variety of fish, the skipjack (bonito), patients with tuberculosis on isoniazid repeatedly developed symptoms very similar to those of histamine poisoning. Skipjack was found to contain probably the highest concentration of histamine reported in fish. Isoniazid is a potent inhibitor of histaminase which normally plays an important role in the metabolism of histamine in the body. It is suggested that the symptoms seen in these patients were, in fact, due to histamine. In these circumstances the high histamine content of skipjack and the interference by isoniazid with the metabolism of the amine presumably play complementary roles in the production of histamine poisoning; each of these factors by itself is apparently inadequate to produce such intoxication. An analysis of the symptoms manifested by 21 patients is presented.

Adolescent↗