Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine

T. Ohrui, K. Yamauchi, K. Sekizawa, Y. Ohkawara, K. Maeyama, M. Sasaki, M. Takemura, H. Wada, T. Watanabe, H. Sasaki, T. Takishima

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    43 Citations (Scopus)

    Abstract

    The contractile response of isolated guinea pig trachea to histamine was potentiated in the presence of the histamine N-methyltransferase (HMT) inhibitor SKF 91488, whereas the diamine oxidase inhibitor aminoguanidine was without effect. SKF 91488 shifted in a concentration-dependent fashion the concentration-response curves to histamine to lower concentrations with the maximum by 1 log unit. The trachea contained significant HMT activity (45.4 ± 5.0 pmol/min/mg protein). In situ hybridization to detect HMT mRNA indicated that HMT mRNA was present in the epithelium and endothelium, being more abundant in the former. Removal of the epithelium shifted the concentration-response curves to histamine to lower concentrations by 0.8 log unit, and SKF 91488 caused only a slight shift of histamine concentration- response curves in tissues denuded of epithelium. These findings suggest that HMT regulates the contractile response of guinea pig trachea to histamine, and epithelial removal-induced bronchial hyperresponsiveness to histamine is largely explained by the loss of HMT in the epithelium.

    Original languageEnglish
    Pages (from-to)1268-1272
    Number of pages5
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume261
    Issue number3
    Publication statusPublished - 1992

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

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