Disease relevance of Hnmt

• 2. After introduction of a prokaryotic expression vector containing the isolated cDNA, Escherichia coli cells expressed histamine N-methyltransferase activity [1].
• Pretreatment of rats with glucocorticoid analog, dexamethasone (DMX), 1 mg/kg of body weight, given twice, 20 and 2 h before decapitation, did not influence significantly the effects invoked by peroxidation on HA levels and the activity of HD and HMT, but impaired histidine transport [2].
• Bilateral injection of the inhibitor of histamine-N-methyltransferase, SKF 91488, which is also known as homodimaprit (5 micrograms), into the preoptic area of the rat produced delayed hypertension, tachycardia and hyperthermia [3].
• Previous study demonstrates that inhibition of histamine N-methyltransferase, which catabolizes histamine released from neurons, leads to the increase in endogenous central histamine concentrations and to the reversal of critical hemorrhagic hypotension [4].
• The findings show changes in histamine levels, histidine decarboxylase and histamine-N-methyltransferase activities in SHR and suggest involvement of histaminergic neurons in hypertension [5].

Psychiatry related information on Hnmt

• The effects of electroconvulsive shock (ECS) on brain histamine (HI) levels, 1-histidine decarboxylase (HD) and HI-methyltransferase (HMT) activities, and H2-receptor--mediated hypothermia were studied in rats [6].

High impact information on Hnmt

• MTF is derived from ND1, a mitochondrially encoded protein, and the amino-terminal N-formyl-methionine is essential for binding to HMT; conservative substitutions at the sixth residue causes MTF to be a minor H antigen [7].
• Whole-body X-irradiation after neonatal injection with N-nitroso-N-ethylurea (ENU) significantly reduced the incidence of induced neurogenic tumors in inbred HMT rats kept for their complete life-span [8].
• Histamine N-methyltransferase from rat kidney. Cloning, nucleotide sequence, and expression in Escherichia coli cells [1].
• Complementary DNA clones encoding rat kidney histamine N-methyltransferase have been isolated using synthetic oligonucleotide probes based on partial amino acid sequences of tryptic peptides of the purified enzyme [1].
• Histamine N-methyltransferase is a major enzyme for inactivating histamine in mammalian tissues [9].

Biological context of Hnmt

• Human histamine N-methyltransferase (HNMT) has a common polymorphism at residue 105 that correlates with the high- (Thr) and low- (Ile) activity phenotypes [10].
• Rat histamine N-methyltransferase. Quantification, tissue distribution, purification, and immunologic properties [9].
• Twenty-four hour rhythms of histamine (H), its biosynthetic enzyme, L-histidine decarboxylase (EC 4.1.1.22, HD) and its inactivation enzyme, histamine N-methyltransferase (EC 2.1.1.8, HMT) were assayed in the 63-day-old male rat hypothalamus using a modified single isotopeenzyme microassay [11].
• These results show that, despite the ability of zolantidine to inhibit HMT in vitro, large doses of this drug did not alter brain HA methylation or turnover in vivo, and they imply that blockade of post-synaptic H2-receptors does not change brain HA dynamics [12].
• Harmaline and a number of other beta-carbolines inhibited HNMT with IC50 values in the range of 1-10 microM [13].

Anatomical context of Hnmt

• We examined in rat cerebral cortex, effects of the following HMT inhibitors (mg/kg i.p.): metoprine (10), tacrine (10), velnacrine (10, 30), and physostigmine (1,2) [14].
• The administration of cocaine (20 mg/kg) increased histamine levels and histamine N-methyltransferase activity in the striatum, nucleus accumbens, and amygdala 1 h later [15].
• The myocyte, for example, was an additional source of HMT activity (1.0 U/mg of protein) in heart [16].
• Purified microvascular endothelial cell preparations from guinea-pig perirenal fat pad, heart ventricles and brain cortex were found to contain high histamine methyltransferase (HMT) activity (4, 3, 4.4 and 1.2 nmol of histamine methylated/hr/mg of protein, respectively) [16].
• HMT was 70% more active in astrocytes than in synaptosomes, whereas HD activity was not different in these two preparations [17].

Associations of Hnmt with chemical compounds

• The facilitatory effect of intra-CA1 histamine was mimicked by the histamine N-methyltransferase inhibitor SKF-91844 as well as by the H2 receptor agonist dimaprit and it was blocked completely by the H2 receptor antagonist ranitidine [18].
• RESULTS: Two ternary structures of human HNMT have been determined: the Thr105 variant complexed with its substrate histamine and reaction product AdoHcy and the Ile105 variant complexed with an inhibitor (quinacrine) and AdoHcy [10].
• CONCLUSIONS: HNMT has a 2 domain structure including a consensus AdoMet binding domain, where the residue 105 is located on the surface, consistent with the kinetic data that the polymorphism does not affect overall protein stability at physiological temperatures but lowers K(M) values for AdoMet and histamine [10].
• Hypothalamic 24-hour rhythms in histamine, histidine, decarboxylase and histamine-N-methyltransferase [11].
• But in brain, histamine is thought to be metabolized solely by histamine methyltransferase (HMT), forming tele-methylhistamine (t-MH) and tele-methylimidazoleacetic acid (t-MIAA) [14].

Other interactions of Hnmt

• A series of base- and amino acid modified analogues of S-aristeromycinyl-L-homocysteine, a carbocyclic nucleoside, were synthesized and evaluated as inhibitors of S-adenosyl-L-methionine-dependent methyltransferases, including catechol O-methyltransferase, phenylethanolamine N-methyltransferase, and histamine N-methyltransferase [19].
• At a dosage of 100 mg/kg (+/-)-alpha-FMH did not alter histamine-N-methyltransferase, DOPA decarboxylase, and glutamate decarboxylase activities [20].
• The liver activities of histamine-metabolizing enzymes, histamine-N-methyltransferase and histaminase, decreased to 1/3.4 and 1/6.0 times those of the nontreated group, respectively, 12 weeks after treatment with CCl4, whereas blood histaminase increased about 9.2 times [21].
• In the cortex-midbrain and brainstem of adult WKY and SHR histidine decarboxylase activity was also increased, while histamine-N-methyltransferase activity was elevated in the cortex-midbrain of adult WKY [5].
• When the enzyme activities are expressed in units per g tissue, the changes in the course of the development of 5 MT-NMT were less apparent, but in any way differed markedly from those of dopa-decarboxylase and histamine N-methyltransferase [22].

Analytical, diagnostic and therapeutic context of Hnmt

• Infusion of prostaglandin E2 (PGE2) into the third cerebroventricle increased the hypothalamic HA turnover rate, and simultaneously activated both HDC and HMT dose-dependently, but intravenous infusion of PGE2 had no effect on the dynamics of hypothalamic HA turnover [23].
• A method for the determination of histamine N-methyltransferase (HMT) activity by high-performance liquid chromatography based on post-column derivatization with omicron-phthalaldehyde is described [24].
• The intensity of the staining in western blotting correlated well with the enzyme activity in all the tissues in these three species, suggesting that our antiserum is useful for quantifying histamine N-methyltransferase protein in rodent tissues [25].
• Northern blotting analysis indicated that the 1.6-kb guinea pig HMT transcript was expressed at various levels in different tissues at the following relative abundance: jejunum, brain > lung, spleen, stomach > liver, kidney [26].
• We can conclude that DAO and HNMT activities in gut mucosa are reliable quantitative markers of acute intestinal allograft rejection in the rat that support histopathological analysis [27].

References