Histamine methylation

The product of histamine methylation, t-MH, is a substrate for MAO-B and is ultimately oxidized to t-MIAA, the end product of brain histamine metabolism. Thus, MAO... 

Animals exposed vivo to cotton dust show similar results. In excised tissues, histamine methylating enzymes fall to zero during exposure, but rise following a rest from cotton dust inhalation. In flax dust exposed animals, histamine activity initially increases.In guinea pigs, enzyme levels fall upon exposure, then rise after removal from exposure. Further, while flax exposed animals show a fall in total lung histamine content, with cotton dust exposure there is an increase. It should, however, be borne in mind that histamine release is not necessarily correlated with total lung histamine (103). 

From Leptodactylus pentadactylus, in addition to spinaceamine and 6-methylspinaceamine, the histidine-related bases histamine, -methyl-histamine, and yv ,A/ -dimethylhistamine (22) were also isolated (Section... 

Leptodactylus pentadactylus and L. ocellatus native to South and Central America, contain considerable amounts of 5-hydroxytryptamine derivatives, like N-methylserotonine, bufotenin and bufotenidin as well as leptodactylin and candicin (ref. 4). Of a new type are substances like histamin, methyl-, and acetyl-histamins, and spinaceamin. Spinaceamin can be synthesized in vitro by a biomimetic reaction of histamin and formaldehyde in aqueous solution at pH 6.8, and room temperature (ref. 5). 

Impromidine is a selective H2 agonist used as a diagnostic aid the potency varies between 9 and 100 times histamine depending on the test system [312, 314,315]. In humans, it produces maximal gastric acid secretion, an effect inhibited by cimetidine [316]. It is a potent inhibitor of histamine methyl transferase and diamine oxidase [315]. The two imidazole units and the... 

In the estimation of unlabelled metabolites extracted from biological materials, enzymes have been used to convert non-radioactive substrates into labelled derivatives. A labelled co-factor is used in a manner similar to the use of a labelled reagent in isotope derivative analysis. A good example of such methods is the double isotope enzymatic assay for histamine [325]. Samples containing unknown amounts of histamine, tracer amounts of H-histamine and " C-S-adenosylmethionine are incubated with a partially purified preparation of histamine methyl transferase from guinea-pig brain. This enzyme is specific for the methylation of histamine [326]. The product of the reaction, 1,4-methylhistamine, is extracted into chloroform and the ratio of determined by liquid scintillation counting, is directly pro-... 

This mechanism takes advantage of the known enhanced susceptibility of methyl sulfonium salts to nucleophilic attack in non-polar media (1, 23). In addition, it allows for the methylation of a soft base, the sulfur atom of methionine, by SAM in a more polar surrounding. Soft bases are known to react readily with methylsulfonium salts in aqueous media (19). The proposed mechanism for histamine methylation is shown in Fig. 2. 

Histamine AND histamine antagonists). It is formed from histidine by the enzyme L-histidine decarboxylase. In the periphery, histamine is stored ia mast cells, basophils, cells of the gastric mucosa, and epidermal cells. In the CNS, histamine is released from nerve cells and acts as a neurotransmitter. The actions of histamine ate terrninated by methylation and subsequent oxidation via the enzymes histamine-/V-methyltransferase and monoamine oxidase. 

In addition, Pfister and coworkers investigated 3-hydroxyflavone-6-carboxylic acids as histamine induced gastric secretion inhibitors. After condensing 3-acetyl-4-hydroxybenzoic acid (45) with a variety of aldehydes 46 to deliver the chalcones 47, these purified chalcones were then subjected to the standard AFO conditions to afford flavonols 48 in 51-80% yield. Subsequent alkylation of 48 with methyl iodide or isopropyl iodide followed by saponification of the corresponding esters gave the target compounds. 

Chloro-oxazolo[4,5-/i]quinoline-2-carboxylic acid methyl ester was the most active compound in tests for inhibitors of antigen-induced release of histamine in vitro from rat peritoneal mast cells (IC50 of 0.3 p,M) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (ED50 (intraperitoneal) of 0.1 mg/kg in dose 0.5 mg/kg as an inhibitor of the test)—10 times and 60 times more potent, respectively, than the disodium salt of cromoglycic acid (85JMC1255). 

Histamine is synthesized from the amino acid histidine via the action of the specific enzyme histidine decarboxylase and can be metabolized by histamine-TV-methyl transferase or diamine oxidase. Interesting, in its role as a neurotransmitter the actions of histamine are terminated by metabolism rather than re-uptake into the pre-synaptic nerve terminals. 

Decarboxylation of histidine to histamine is catalyzed by a broad-specificity aromatic L-amino acid decarboxylase that also catalyzes the decarboxylation of dopa, 5-hy-droxytryptophan, phenylalanine, tyrosine, and tryptophan. a-Methyl amino acids, which inhibit decarboxylase activity, find appfication as antihypertensive agents. Histidine compounds present in the human body include ergothioneine, carnosine, and dietary anserine (Figure 31-2). Urinary levels of 3-methylhistidine are unusually low in patients with Wilson s disease. 

Histamine is synthesised by decarboxylation of histidine, its amino-acid precursor, by the specific enzyme histidine decarboxylase, which like glutaminic acid decarboxylase requires pyridoxal phosphate as co-factor. Histidine is a poor substrate for the L-amino-acid decarboxylase responsible for DA and NA synthesis. The synthesis of histamine in the brain can be increased by the administration of histidine, so its decarboxylase is presumably not saturated normally, but it can be inhibited by a fluoromethylhistidine. No high-affinity neuronal uptake has been demonstrated for histamine although after initial metabolism by histamine A-methyl transferase to 3-methylhistamine, it is deaminated by intraneuronal MAOb to 3-methylimidazole acetic acid (Fig. 13.4). A Ca +-dependent KCl-induced release of histamine has been demonstrated by microdialysis in the rat hypothalamus (Russell et al. 1990) but its overflow in some areas, such as the striatum, is neither increased by KCl nor reduced by tetradotoxin and probably comes from mast cells. 

A series of novel l-substituted-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-ones 1 were synthesized by the cyclization of 2-hydrazino-3-phenyl-quinazolin-4(3H) 2 with various one carbon donors. The starting material 2-hydrazino-3-phenylquinazolin-4(3H)-one 2, was synthesized from aniline 7 by a novel innovative route. When tested for their in vivo Hi-antihistaminic activity on conscious guinea pigs all the test compounds protected the animals from histamine-induced bronchospasm significantly, whereas the compound l-methyl-4-phenyl-l,2,3-triazolo(4,3-a)quinazolin-5(4H)-one lb (percentage protection 70.7%) was found to be equipotent with the reference standard chlorpheniramine maleate (percentage protection 71%). These compounds show negligible sedation (5%) when compared to the reference standard (26%). Hence they could serve as prototype molecules for future development [1,4,5]. 

The group C counterirritants methyl nicotinate and histamine dihydrochloride produce vasodilation.24 Methyl nicotinate is a nicotinic acid derivative that produces prostaglandin-mediated vasodilation.46 NSAIDs and aspirin block the production of prostaglandins and decrease methyl nicotinate-induced vasodilation. Application over a large area has been reported to cause systemic symptoms and syncope, possibly due to vasodilation and a decrease in blood pressure.47 Patients should be educated to apply only scant amounts to the affected area to avoid this effect. 

HA turnover is rapid in the brain, with a half-life of about 30 min. This can change very quickly depending on neuronal activity. There is no high-affinity uptake system for HA once released, HA is inactivated by catabolism. In the brain, released HA is methylated almost exclusively by the enzyme histamine-N-methyltransferase (E.C. 2.1.1.8). The tele-methyl-HA is subsequently degraded by monoamine oxidase-B (MAO-B) and aldehyde dehydrogenase to produce tele-methylimidazoleacetic acid (Brown et ah, 2001). 

OCTs) tyramine, tryptamine, N-methylnico-tineamide (NMN), choline, spermine, spermidine quinine, d-tubocurarine, procanamide, dopamine, noradrenaline, serotonin, histamine, corticosterone, l-methyl-4-phenylpyridinium (MPP), despramine... 

The PCBM methyl ester can be used for coupling amine-containing ligands after removal of the methyl group and activation of the carboxylate using a number of different reaction strategies. Hummelen et al. (1995) successfully coupled cholestanol and histamine to the fuller-ene-PCBM derivative (after acid chloride formation) for use in fabrication of photodetectors and biological studies, respectively. For specific applications of PCBM-fullerenes, see Shaheen et al. (2001), Brabec et al. (2001), Yu et al. (1995), Mecher et al. (2002), Meijer et al. (2003), van Duren et al. (2004), and Anthopoulos et al. (2004). 

Histamine synthesis in the brain is controlled by the availability of L-histidine and the activity of histidine decarboxylase 254 Histamine is stored within and released from neurons but a neuronal transporter for histamine has not been found 254 In the vertebrate brain, histamine metabolism occurs predominately by methylation 254... 

Neuronal histamine can be methylated outside of histaminergic nerve terminals 254... 

Biosynthesis is performed in one step by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). Histamine metabolism occurs mainly by two pathways. Oxidation is carried out by diamine oxidase (DAO, E.C. 1.4.3.6), leading to imidazole acetic acid (IAA), whereas methyla-tion is effected by histamine N-methyltransferase (HMT, E.C. 2.1.1.8), producing fe/e-methylhistamine (t-MH). IAA can exist as a riboside or ribotide conjugate. t-MH is further metabolized by monoamine oxidase (MAO)-B, producing fe/e-methylimidazole acetic acid (t-MIAA). Note that histamine is a substrate for DAO but not for MAO. Aldehyde intermediates, formed by the oxidation of both histamine and t-MH, are thought to be quickly oxidized to acids under normal circumstances. In the vertebrate CNS, histamine is almost exclusively methylated... 

Neuronal histamine can be methylated outside of histaminergic nerve terminals. In contrast to the striking regional distribution of histamine and HDC, HMT shows a more even distribution [14], suggesting a widespread HMT localization. In support of this, lesions that destroy... 

Takemura, M., Tanaka, T., Taguchi, Y. etal. Histamine N-methyl transferase from rat kidney. J. Biol. Chem. 267 15687-15691,1992. 

A high intracerebral level of S-adenosylhomocysteine may inhibit methylation reactions involving S-adenosyl-methionine. The metabolic repercussions would be extensive, including deficient methylation of proteins and of phos-phatidylethanolamine as well as an inhibition of catechol-O-methyltransferase and histamine-N-methyltransferase. 

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