Structure and function of human histamine N-methyltransferase: Critical enzyme in histamine metabolism in airway

K. Yamauchi, K. Sekizawa, H. Suzuki, H. Nakazawa, Y. Ohkawara, D. Katayose, H. Ohtsu, G. Tamura, S. Shibahara, M. Takemura, K. Maeyama, T. Watanabe, H. Sasaki, K. Shirato, T. Takishima

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In mammals, histamine is inactivated principally by two enzymes: histamine N-methyl-transferase (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 analysis with hHMT cDNA probe revealed that 1.6-kb HMT mRNA transcript was expressed in the lung, nasal polyps, and kidney. HMT activity was measured in human trachea and bronchi. In addition, the contractile response of isolated human bronchi to histamine was potentiated in the presence of an HMT inhibitor, SKF 91488, but a DAO inhibitor, aminoguanidine, was without effect. These results suggest that HMT plays an important role in degrading histamine and in regulating the airway response to histamine. Therefore, the level of HMT gene expression in human airway may be one of the critical factors determining the airway responsiveness to histamine. In situ chromosomal hybridization demonstrated that human HMT gene was localized in chromosome 1 p32.

元の言語English
ページ(範囲)L342-L349
ジャーナルAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
267
発行部数3 11-3
DOI
出版物ステータスPublished - 1994

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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    Yamauchi, K., Sekizawa, K., Suzuki, H., Nakazawa, H., Ohkawara, Y., Katayose, D., Ohtsu, H., Tamura, G., Shibahara, S., Takemura, M., Maeyama, K., Watanabe, T., Sasaki, H., Shirato, K., & Takishima, T. (1994). 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(3 11-3), L342-L349. https://doi.org/10.1152/ajplung.1994.267.3.l342