Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo

K. Sekizawa, H. Nakazawa, T. Ohrui, K. Yamauchi, Y. Ohkawara, K. Maeyama, T. Watanabe, H. Sasaki, T. Takishima

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    Abstract

    To examine whether histamine N-methyltransferase (HMT; EC 2.1.1.8) modulates the effects of allergic reaction in vivo, we studied the effects of aerosolized SKF 91488, a specific HMT inhibitor, on the responses to aerosolized histamine in unsensitized guinea pigs and to ovalbumin (OA) antigen inhalation in guinea pigs sensitized to OA. Airway responsiveness was assessed by determining provocation concentrations of histamine and OA aerosols that increased pulmonary resistance to twice the baseline values. SKF 94188 shifted, in a dose-dependent fashion, the dose-response curves to histamine and OA antigen to lower concentrations, and it significantly decreased provocation concentrations of both histamine and OA antigen (p < 0.01). In contrast of SKF 91488, aerosolized aminoguanidine, a specific inhibitor of diamine oxidase (10-2 M, 90 breaths), did not alter the provocation concentration of histamine (p > 0.20). SKF 91488 (10-2 M, 90 breaths) caused no significant changes in response to acetylcholine (p > 0.30). HMT activities were observed in the entire airways of the trachea, main bronchi, segmental bronchi and bronchioles, and parenchymal tissues. These findings suggest that HMT modulates the effects of exogenous histamine and endogenously released histamine by antigen challenge on bronchoconstrictor responses in guinea pigs in vivo.

    Original languageEnglish
    Pages (from-to)92-96
    Number of pages5
    JournalAmerican Review of Respiratory Disease
    Volume147
    Issue number1
    DOIs
    Publication statusPublished - 1993 Jan 1

    ASJC Scopus subject areas

    • Pulmonary and Respiratory Medicine

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  • Cite this

    Sekizawa, K., Nakazawa, H., Ohrui, T., Yamauchi, K., Ohkawara, Y., Maeyama, K., Watanabe, T., Sasaki, H., & Takishima, T. (1993). Histamine N-methyltransferase modulates histamine- and antigen-induced bronchoconstriction in guinea pigs in vivo. American Review of Respiratory Disease, 147(1), 92-96. https://doi.org/10.1164/ajrccm/147.1.92