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1

Yoshikawa, Takeo, Tadaho Nakamura, and Kazuhiko Yanai. "Histamine N-Methyltransferase in the Brain." International Journal of Molecular Sciences 20, no. 3 (2019): 737. http://dx.doi.org/10.3390/ijms20030737.

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Brain histamine is a neurotransmitter and regulates diverse physiological functions. Previous studies have shown the involvement of histamine depletion in several neurological disorders, indicating the importance of drug development targeting the brain histamine system. Histamine N-methyltransferase (HNMT) is a histamine-metabolising enzyme expressed in the brain. Although pharmacological studies using HNMT inhibitors have been conducted to reveal the direct involvement of HNMT in brain functions, HNMT inhibitors with high specificity and sufficient blood–brain barrier permeability have not be
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2

Futo, Judit, Josh P. Kupferberg, Jonathan Moss, Mark R. Fahey, John E, and Ronald D. Miller. "Vecuronium Inhibits Histamine N-Methyltransferase." Anesthesiology 69, no. 1 (1988): 92–96. http://dx.doi.org/10.1097/00000542-198807000-00014.

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3

Moss, J., K. M. Verburg, and D. P. Henry. "DROPERIDOL INHIBITS HISTAMINE N-METHYLTRANSFERASE." Anesthesiology 63, Supplement (1985): A303. http://dx.doi.org/10.1097/00000542-198509001-00303.

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4

Weinshilboum, Richard M., Diane M. Otterness, and Carol L. Szumlanski. "METHYLATION PHARMACOGENETICS: Catechol O-Methyltransferase, Thiopurine Methyltransferase, and Histamine N-Methyltransferase." Annual Review of Pharmacology and Toxicology 39, no. 1 (1999): 19–52. http://dx.doi.org/10.1146/annurev.pharmtox.39.1.19.

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5

McClain, Jonathon L., Wilmarie Morales-Soto, Jacques Gonzales, Visha Parmar, Elena Y. Demireva, and Brian D. Gulbransen. "Sexually Dimorphic Effects of Histamine Degradation by Enteric Glial Histamine N-Methyltransferase (HNMT) on Visceral Hypersensitivity." Biomolecules 13, no. 11 (2023): 1651. http://dx.doi.org/10.3390/biom13111651.

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Histamine is a neuromodulator that affects gut motility and visceral sensitivity through intrinsic and extrinsic neural pathways, yet the mechanisms regulating histamine availability in these pathways remain poorly understood. Here, we show that enteric glia contribute to histamine clearance in the enteric nervous system (ENS) through their expression of the enzyme histamine N-methyltransferase (HNMT). Glial HNMT expression was initially assessed using immunolabeling and gene expression, and functionally tested using CRISPR-Cas9 to create a Cre-dependent conditional Hnmt ablation model targeti
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6

Tamaoki, J., A. Chiyotani, E. Tagaya, K. Isono, and K. Konno. "Histamine N-methyltransferase Modulates Human Bronchial Smooth Muscle Contraction." Mediators of Inflammation 3, no. 2 (1994): 125–29. http://dx.doi.org/10.1155/s0962935194000153.

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To elucidate the modulatory role of histamine-degrading enzymes in airway constrictor responses, human bronchial strips were studied under isometric conditionsin vitro. Pretreatment of tissues with the histamine N-methyltransferase (HMT) inhibitor SKF 91488 specifically potentiated the contractile responses to histamine, causing a leftward displacement of the concentration response curves, whereas the diamine oxidase inhibitor aminoguanidine had no effect. This potentiation was attenuated by mechanical removal of the epithelium. The HMT activity was detected in the human bronchi, which was les
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7

Gitomer, W. L., and K. F. Tipton. "Purification and kinetic properties of ox brain histamine N-methyltransferase." Biochemical Journal 233, no. 3 (1986): 669–76. http://dx.doi.org/10.1042/bj2330669.

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Histamine N-methyltransferase (EC 2.1.1.8) was purified 1100-fold from ox brain. The native enzyme has an Mr of 34800 +/- 2400 as measured by gel filtration on Sephadex G-100. The enzyme is highly specific for histamine. It does not methylate noradrenaline, adrenaline, DL-3,4-dihydroxymandelic acid, 3,4-dihydroxyphenylacetic acid, 3-hydroxytyramine or imidazole-4-acetic acid. Unlike the enzyme from rat and mouse brain, ox brain histamine N-methyltransferase did not exhibit substrate inhibition by histamine. Initial rate and product inhibition studies were consistent with an ordered steady-stat
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8

Harvima, Rauno J., Ilkka T. Harvima, and Jorma E. Fräki. "Optimization of histamine radio enzyme assay with purified histamine-N-methyltransferase." Clinica Chimica Acta 171, no. 2-3 (1988): 247–56. http://dx.doi.org/10.1016/0009-8981(88)90150-7.

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9

Lamberti, C., A. Bartolini, C. Ghelardini, and P. Malmberg-Aiello. "Histamin H1-antagonists antinociception in mice and inhibition of histamine-N-methyltransferase." Pharmacological Research 31 (January 1995): 258. http://dx.doi.org/10.1016/1043-6618(95)87292-2.

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10

Kitano, Haruna, Takeo Yoshikawa, and Kazuhiko Yanai. "Drug development targeting histamine N-methyltransferase." Proceedings for Annual Meeting of The Japanese Pharmacological Society 92 (2019): 1—P—006. http://dx.doi.org/10.1254/jpssuppl.92.0_1-p-006.

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11

Wollin, A. "Uptake and methylation of histamine by dispersed gastric mucosal cells and its possible influence on acid secretion." Canadian Journal of Physiology and Pharmacology 68, no. 1 (1990): 71–78. http://dx.doi.org/10.1139/y90-010.

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Inactivation of histamine by gastric mucosal tissue was examined in dispersed rabbit gastric mucosal cells. Mucosal cells were incubated with [14C]histamine. The formed radioactive metabolites were separated and identified by thin layer co-chromatography and quantitated, in both the cellular and extracellular mediums. Gastric mucosal cells internalized histamine, most of which was immediately methylated primarily to Nτ-methylhistamine and released. Cellular histamine product accumulation reached a plateau. The rate of histamine methylation increased with increasing extracellular histamine conc
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12

Tamaoki, Jun, Minako Araake, Atsushi Chiyotani, Kazuo Isono, and Atsushi Nagai. "Airway hyperresponsiveness to histamine in mycoplasmal infection: role of histamine N-methyltransferase." European Journal of Pharmacology 347, no. 2-3 (1998): 257–60. http://dx.doi.org/10.1016/s0014-2999(98)00177-0.

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13

Kitanaka, Junichi, Nobue Kitanaka, Tohru Tsujimura, Nobuyuki Terada, and Motohiko Takemura. "Histamine N-methyltransferase regulates histamine-induced phosphoinositide hydrolysis in guinea pig cerebellum." Neuroscience Letters 308, no. 1 (2001): 5–8. http://dx.doi.org/10.1016/s0304-3940(01)01947-4.

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14

Drozak, Jakub, Lukasz Chrobok, Olga Poleszak, Adam K. Jagielski, and Rafal Derlacz. "Molecular Identification of Carnosine N-Methyltransferase as Chicken Histamine N-Methyltransferase-Like Protein (HNMT-Like)." PLoS ONE 8, no. 5 (2013): e64805. http://dx.doi.org/10.1371/journal.pone.0064805.

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15

Yoshikawa, Takeo, Rina Otsuka, Yuki Sato, and Kazuhiko Yanai. "Development of Histamine N-methyltransferase Inhibitors for Brain Disorders." Proceedings for Annual Meeting of The Japanese Pharmacological Society 94 (2021): 3—P1–36. http://dx.doi.org/10.1254/jpssuppl.94.0_3-p1-36.

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16

Matuszewska, Bozena, and Ronald T. Borchardt. "Rat Kidney Histamine N-Methyltransferase: Purification and Partial Characterization." Preparative Biochemistry 15, no. 3 (1985): 145–57. http://dx.doi.org/10.1080/10826068508062268.

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17

Kitanaka, Junichi, Nobue Kitanaka, Tatsuya Tanaka, and Motohiko Takemura. "cDNA cloning of the guinea pig histamine N-methyltransferase." Japanese Journal of Pharmacology 82 (2000): 124. http://dx.doi.org/10.1016/s0021-5198(19)47959-6.

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18

Pacifici, G. M., P. Donatelli, and L. Giuliani. "Histamine N-methyltransferase in humans tissues: inhibition fey chloroquine." European Journal of Pharmacology 183, no. 5 (1990): 1647. http://dx.doi.org/10.1016/0014-2999(90)91936-6.

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19

Ohrui, T., K. Yamauchi, K. Sekizawa, et al. "Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine." Journal of Pharmacology and Experimental Therapeutics 261, no. 3 (1992): 1268–72. https://doi.org/10.1016/s0022-3565(25)11148-8.

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20

Sekizawa, K., H. Nakazawa, T. Ohrui, et al. "Histamine N-Methyltransferase Modulates Histamine- and Antigen-induced Bronchoconstriction in Guinea PigsIn Vivo." American Review of Respiratory Disease 147, no. 1 (1993): 92–96. http://dx.doi.org/10.1164/ajrccm/147.1.92.

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21

Yamauchi, K., K. Sekizawa, H. Suzuki, et al. "Structure and function of human histamine N-methyltransferase: critical enzyme in histamine metabolism in airway." American Journal of Physiology-Lung Cellular and Molecular Physiology 267, no. 3 (1994): L342—L349. http://dx.doi.org/10.1152/ajplung.1994.267.3.l342.

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In mammals, histamine is inactivated principally by two enzymes: histamine N-methyltransferase (HMT; EC 2.1.1.8) and diamine oxidase (DAO; EC 1.4.3.6.). The cDNA clone of human HMT (hHMT) has been isolated from a cDNA library of human kidney and its nucleotide, and deduced amino acid sequences have been determined. One clone, phHMT-1, containing an insert of 1.4 kb, was confirmed to encode HMT by transient expression of HMT activity in COS cells. hHMT consists of 292 amino acid residues [relative molecular weight (M(r)) = 33,279] and shares 82% identity with that of rat HMT. Northern blot anal
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22

Junichi, Kitanaka. "How the histamine N-methyltransferase inhibitor metoprine alleviates methamphetamine reward." Journal of Addiction Medicine and Therapeutic Science 3, no. 2 (2017): 016–23. https://doi.org/10.17352/2455-3484.000021.

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Methamphetamine (METH) is a highly addictive psychomotor stimulant drug that is abused worldwide [1]. METH abuse results in numerous adverse effects after acute administration, as well as an array of adverse outcomes associated with binge use, long-term use, and withdrawal [2-4]. Acutely METH releases dopamine from synaptic terminals through multiple actions that include inducing reverse transport of dopamine via the dopamine transporter (DAT), impairing the function of the vesicular monoamine transporter-2 (VMAT2), leading to increased cytoplasmic dopamine concentrations, and inhibition of mo
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23

Flores-Clemente, Cecilia, María Inés Nicolás-Vázquez, Elvia Mera Jiménez, and Maricarmen Hernández-Rodríguez. "Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer’s Disease." Biomolecules 11, no. 10 (2021): 1408. http://dx.doi.org/10.3390/biom11101408.

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Alzheimer’s disease (AD) represents the principal cause of dementia among the elderly. Great efforts have been established to understand the physiopathology of AD. Changes in neurotransmitter systems in patients with AD, including cholinergic, GABAergic, serotoninergic, noradrenergic, and histaminergic changes have been reported. Interestingly, changes in the histaminergic system have been related to cognitive impairment in AD patients. The principal pathological changes in the brains of AD patients, related to the histaminergic system, are neurofibrillary degeneration of the tuberomammillary
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24

Otsuka, Rina, Fumito Naganuma, Tadaho Nakamura, et al. "Contribution of astrocytic histamine N-methyltransferase to histamine clearance and brain function in mice." Neuropharmacology 212 (July 2022): 109065. http://dx.doi.org/10.1016/j.neuropharm.2022.109065.

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25

Otsuka, Rina, Fumito Naganuma, Tadaho Nakamura, et al. "Contribution of astrocytic histamine N-methyltransferase to histamine clearance and brain function in mice." Neuropharmacology 212 (July 2022): 109065. http://dx.doi.org/10.1016/j.neuropharm.2022.109065.

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26

Hon, Yuen Yi, William J. Jusko, Hong-Hao Zhou, et al. "Endogenous Histamine and Cortisol Levels in Subjects with Different Histamine N-Methyltransferase C314T Genotypes." Molecular Diagnosis & Therapy 10, no. 2 (2006): 109–14. http://dx.doi.org/10.1007/bf03256450.

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27

Prast, H., V. Gujrati, S. Walser, and A. Philippu. "Histamine, histidine decarboxylase and histamine-N-methyltransferase in brain areas of spontaneously hypertensive rats." Naunyn-Schmiedeberg's Archives of Pharmacology 338, no. 5 (1988): 573–76. http://dx.doi.org/10.1007/bf00179332.

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28

Scott, Mary C., Jon A. Van Loon, and Richard M. Weinshilboum. "Pharmacogenetics of N-methylation: Heritability of human erythrocyte histamine N-methyltransferase activity." Clinical Pharmacology and Therapeutics 43, no. 3 (1988): 256–62. http://dx.doi.org/10.1038/clpt.1988.30.

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29

Yoshikawa, Takeo, Yurika Komatsu, Kensuke Matsuzawa, et al. "Important role of neuronal histamine N-methyltransferase in brain functions." Proceedings for Annual Meeting of The Japanese Pharmacological Society 95 (2022): 1—O—001. http://dx.doi.org/10.1254/jpssuppl.95.0_1-o-001.

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30

Palada, Vinko, Janoš Terzić, Joseph Mazzulli, et al. "Histamine N-methyltransferase Thr105Ile polymorphism is associated with Parkinson's disease." Neurobiology of Aging 33, no. 4 (2012): 836.e1–836.e3. http://dx.doi.org/10.1016/j.neurobiolaging.2011.06.015.

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31

Tahara, Akihito, Masahiro Nishibori, Ken Sawada, Junko Sakiyama, and Kiyomi Saeki. "Localization of histamine N-methyltransferase in guinea pig peripheral tissues." Japanese Journal of Pharmacology 82 (2000): 124. http://dx.doi.org/10.1016/s0021-5198(19)47958-4.

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32

Kitanaka, Junichi, Nobue Kitanaka, Tohru Tsujimura, Michiko Kakihana, Nobuyuki Terada, and Motohiko Takemura. "Guinea Pig Histamine N-Methyltransferase: cDNA Cloning and mRNA Distribution." Japanese Journal of Pharmacology 85, no. 1 (2001): 105–8. http://dx.doi.org/10.1254/jjp.85.105.

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33

HARVIMA, R., E. OLAVIKAJANDER, I. HARVIMA, and J. FRAKI. "Purification and partial characterization of rat kidney histamine-N-methyltransferase." Biochimica et Biophysica Acta (BBA) - General Subjects 841, no. 1 (1985): 42–49. http://dx.doi.org/10.1016/0304-4165(85)90272-7.

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34

Harle, D. G., B. A. Baldo, and M. M. Fisher. "Inhibition of histamine-N-methyltransferase activity by neuromuscular blocking drugs." Agents and Actions 17, no. 1 (1985): 27–31. http://dx.doi.org/10.1007/bf01966676.

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35

Van Loon, Jon A., Patricio A. Pazmiño, and Richard M. Weinshilboum. "Human erythrocyte histamine N-methyltransferase: radiochemical microassay and biochemical properties." Clinica Chimica Acta 149, no. 2-3 (1985): 237–51. http://dx.doi.org/10.1016/0009-8981(85)90337-7.

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36

Yan, Lan, Carol L. Szumlanski, Sharmon R. Rice, Janet L. Sobell, Herbert M. Lachman, and Richard M. Weinshilboum. "Histamine N-methyltransferase functional polymorphism: Lack of association with schizophrenia." American Journal of Medical Genetics 96, no. 3 (2000): 404–6. http://dx.doi.org/10.1002/1096-8628(20000612)96:3<404::aid-ajmg31>3.0.co;2-d.

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37

Fukuda, Hiroshi, Atsushi Yamatodani, Ikuo Imamura, Kazutaka Maeyama, Takehiko Watanabe, and Hiroshi Wada. "High-performance liquid chromatographic determination of histamine N-methyltransferase activity." Journal of Chromatography B: Biomedical Sciences and Applications 567, no. 2 (1991): 459–64. http://dx.doi.org/10.1016/0378-4347(91)80152-3.

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38

Sekizawa, Kiyohisa, Hideki Nakazawa, Masatoshi Morikawa, et al. "Histamine N-methyltransferase inhibitor potentiates histamine- and antigen-induced airway microvascular leakage in guinea pigs." Journal of Allergy and Clinical Immunology 96, no. 6 (1995): 910–16. http://dx.doi.org/10.1016/s0091-6749(95)70228-8.

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39

Girard, B., D. M. Otterness, T. C. Wood, R. Honchel, E. D. Wieben, and R. M. Weinshilboum. "Human histamine N-methyltransferase pharmacogenetics: cloning and expression of kidney cDNA." Molecular Pharmacology 45, no. 3 (1994): 461–68. https://doi.org/10.1016/s0026-895x(25)10018-7.

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40

Takahashi, Yuna, Takeo Yoshikawa, Rina Otsuka, and Kazuhiko Yanai. "Role of astrocytic histamine N-methyltransferase in brain functions." Proceedings for Annual Meeting of The Japanese Pharmacological Society 93 (2020): 1—LBS—03. http://dx.doi.org/10.1254/jpssuppl.93.0_1-lbs-03.

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41

Okayama, Michiko, Kohei Yamauchi, Kiyohisa Sekizawa, et al. "Localization of histamine N-methyltransferase messenger RNA in human nasal mucosa." Journal of Allergy and Clinical Immunology 95, no. 1 (1995): 96–102. http://dx.doi.org/10.1016/s0091-6749(95)70157-5.

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42

Preuss, Charles V., Thomas C. Wood, Carol L. Szumlanski, et al. "Human Histamine N-Methyltransferase Pharmacogenetics: Common Genetic Polymorphisms that Alter Activity." Molecular Pharmacology 53, no. 4 (1998): 708–17. http://dx.doi.org/10.1124/mol.53.4.708.

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43

NISHIBORI, M., R. OISHI, Y. ITOH, and K. SAEKI. "Purification and partial characterization of histamine N-methyltransferase from bovine brain." Neurochemistry International 19, no. 1-2 (1991): 135–41. http://dx.doi.org/10.1016/0197-0186(91)90128-z.

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44

Horton, John R., Ken Sawada, Masahiro Nishibori, and Xiaodong Cheng. "Structural Basis for Inhibition of Histamine N-Methyltransferase by Diverse Drugs." Journal of Molecular Biology 353, no. 2 (2005): 334–44. http://dx.doi.org/10.1016/j.jmb.2005.08.040.

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45

Harle, David G., and Brian A. Baldo. "Structural features of potent inhibitors of rat kidney histamine N-methyltransferase." Biochemical Pharmacology 37, no. 3 (1988): 385–88. http://dx.doi.org/10.1016/0006-2952(88)90203-1.

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46

Futo, Judit, Josh P. Kupferberg, and Jonathan Moss. "Inhibition of histamine N-methyltransferase (HNMT) in vitro by neuromuscular relaxants." Biochemical Pharmacology 39, no. 3 (1990): 415–20. http://dx.doi.org/10.1016/0006-2952(90)90045-m.

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47

Kitanaka, Nobue, Junichi Kitanaka, Tetsuya Oue, Yoshihiko Tada, Tatsuya Tanaka, and Motohiko Takemura. "Genomic Structure of the Rat and Mouse Histamine N-Methyltransferase Gene." Japanese Journal of Pharmacology 88, no. 1 (2002): 85–92. http://dx.doi.org/10.1254/jjp.88.85.

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48

Feurle, J., S. Rajtar, T. Irman-Florjanc, and H. G. Schwelberger. "Molecular cloning of guinea-pig diamine oxidase and histamine N-methyltransferase." Inflammation Research 55, S1 (2006): S59—S60. http://dx.doi.org/10.1007/s00011-005-0042-0.

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49

Kang, M., H. Yoshimatsu, S. Chiba, et al. "Hypothalamic neuronal histamine modulates physiological responses induced by interleukin-1 beta." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 269, no. 6 (1995): R1308—R1313. http://dx.doi.org/10.1152/ajpregu.1995.269.6.r1308.

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Dynamic involvement of hypothalamic histamine in ingestive behavior and thermogenesis induced by interleukin-1 beta (IL-1 beta) was examined in rats. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta decreased food and water intake and elevated body temperature. However, depletion of neuronal histamine induced by intraperitoneal injection of 160 mumol/rat alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the suppressive effect on drinking, and enhanced the elevating effect on rectal t
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50

Otsuka, Rina, Fumito Naganuma, Yuki Sato, Yuna Takahashi, Kazuhiko Yanai, and Takeo Yoshikawa. "Astrocytic histamine N-methyltransferase controls locomotor activity and vigilance state." Proceedings for Annual Meeting of The Japanese Pharmacological Society 94 (2021): 1—O—B3–2. http://dx.doi.org/10.1254/jpssuppl.94.0_1-o-b3-2.

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