Disease relevance of HNMT

• HMT and histaminase activities were determined in 15 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate obtained during surgical therapy [1].
• OBJECTIVE: This study aims to determine whether there exists a relationship between HNMT gene polymorphisms and the risk for gastric ulcer (GU) [2].
• Severity of ulcerative colitis is associated with a polymorphism at diamine oxidase gene but not at histamine N-methyltransferase gene [3].
• Thus, septic shock patients may have a circulating inhibitor of the HNMT enzyme, but plasma histamine concentrations are normal [4].
• Histamine N-methyltransferase and diamine oxidase gene polymorphisms in patients with inflammatory and neoplastic intestinal diseases [5].

Psychiatry related information on HNMT

• The histamine receptor H1 antagonist diphenhydramine, the antimalarial drug amodiaquine, the antifolate drug metoprine, and the anticholinesterase drug tacrine (an early drug for Alzheimer's disease) are surprisingly all potent HNMT inhibitors, having inhibition constants in the range of 10-100nM [6].
• The availability of this assay will make it possible to test the hypothesis that individual variations in RBC HNMT activity might be used to predict individual differences in HNMT activity in other human cells and tissues [7].
• Human brain cytosolic histamine-N-methyltransferase is decreased in Down syndrome and increased in Pick's disease [8].

High impact information on HNMT

• We have examined DNA repair in the dihydrofolate reductase (DHFR) gene in cultured human cells treated with 4'-hydroxymethyl-4,5',8-trimethylpsoralen (HMT) using a newly developed assay for interstrand DNA cross-linking in defined genomic sequences [9].
• Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase [10].
• Increased Suv39h1 expression repressed MyoD-dependent muscle gene expression and this property required its HMT activity [11].
• Suv39h1 is a histone H3 lysine-9 (H3-K9) specific methyltransferase (HMT) that is associated with gene silencing through chromatin modification [11].
• A flurry of recent papers now describe a third class of HMT that affects chromatin silencing indirectly, not by methylation of histone tails, but instead by targeting a conserved lysine residue in the core domain of the nucleosome [12].

Chemical compound and disease context of HNMT

• If the adverse effects of chloroquine are due to the inhibition of histamine N-methyltransferase, therapy with the l-enantiomer might have lower toxicity [13].

Biological context of HNMT

• In agreement with the predominant role of ABP1 versus HNMT on local histamine metabolism in human bowel, the frequencies for carriers of HNMT genotypes or mutated alleles were similar among patients, regardless clinical evolution, and control individuals [3].
• Therefore, the level of HMT gene expression in human airway may be one of the critical factors determining the airway responsiveness to histamine [14].
• In situ chromosomal hybridization demonstrated that human HMT gene was localized in chromosome 1 p32 [14].
• These observations will make it possible to test the hypothesis that genetic polymorphisms for HNMT may play a role in the pathophysiology of human disease [15].
• IC50 values for the HNMT inhibitor amodiaquine were 0.50, 0.48, and 0.40 microM, respectively, for enzyme from these same three sources [16].

Anatomical context of HNMT

• HDC activity was found in WM35 and WM983 cell lines, while detectable HNMT activity was measured in WM983, M1 and HT168 lines [17].
• Increases in the histamine content and HDC and HMT activities were observed in the nasal mucosa and lung of TDI-sensitized guinea pigs [18].
• HMT activity was measured in human trachea and bronchi [14].
• The level of HNMT activity in human red blood cells is controlled by a common genetic polymorphism [16].
• COS-1 cells transfected with the Ile105 allele had significantly lower HNMT activity and immunoreactive HNMT protein than did those transfected with the Thr105 allele [15].

Associations of HNMT with chemical compounds

• Human renal cortical HNMT, partially purified human renal cortical HNMT, and partially purified transfected COS-1 cell HNMT had Km values for histamine and S-adenosyl-L-methionine, the two cosubstrates for the enzyme reaction, of 20, 13, and 14 microM and 2.0, 3.0, and 6.2 microM, respectively [16].
• Antimalarial drugs that inhibit histamine N-methyltransferase also inhibit putrescine catabolism in vivo and DAO activity in vitro [19].
• It was determined that vecuronium is a strong inhibitor of HNMT; apparent Ki = 1 microM [20].
• Therefore, we performed in vitro kinetic studies of purified HNMT to determine the effects of the steroidal and curare-like NMRs and also of gallamine on histamine catabolism [21].
• 3. The activities of catechol methyltransferase and thiopurine methyltransferase were measured in the renal cortex and any correlations with HNMT activity were assessed [22].

Regulatory relationships of HNMT

• Histidine decarboxylase and histamine N-methyltransferase activities are enhanced by gastrin, but are not influenced by vagal stimulation [23].

Other interactions of HNMT

• The activities of three methylating enzymes HIOMT, COMT, and HNMT were determined in pineal glands from 2 groups of adult vizcachas of both sexes, one (I) maintained under permanent lighting (15 days) and the other (II) kept in darkness [24].
• DNA was isolated from 12 kidney samples with widely different HNMT phenotypes, and exons of the HNMT gene were amplified with the polymerase chain reaction [15].
• OBJECTIVE: The objective was to compare the expression of HDC mRNA and HMT mRNA in nasal mucosa with normal individuals and patients with allergic rhinitis [25].
• Pharmacogenetic studies of methyltransferase enzymes have resulted in the identification and characterization of functionally important common genetic polymorphisms for catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase [10].
• Histamine N-methyltransferase (HNMT) is believed to be the sole pathway for termination of the neurotransmitter action of histamine in mammalian brain [26].

Analytical, diagnostic and therapeutic context of HNMT

• Northern blot analysis with hHMT cDNA probe revealed that 1.6-kb HMT mRNA transcript was expressed in the lung, nasal polyps, and kidney [14].
• Structural characterization of the HNMT gene was performed by use of a polymerase chain reaction (PCR)-based strategy [27].
• HDC, HMT and beta-actin mRNA were amplified by reverse transcription-polymerase chain reaction (RT-PCR) [25].
• HNMT was purified by sequential ion exchange, hydrophobic and molecular exclusion chromatography [28].
• Limited specific digestion and two-dimensional gel electrophoresis yield fragments cross-linked by HMT [29].

References