J. Tamaoki et al., HISTAMINE N-METHYLTRANSFERASE MODULATES HUMAN BRONCHIAL SMOOTH-MUSCLECONTRACTION, Mediators of inflammation, 3(2), 1994, pp. 125-129
To elucidate the modulatory role of histamine-degrading enzymes in air
way constrictor responses, human bronchial strips were studied under i
sometric conditions in vitro. Pretreatment of tissues with the histami
ne N-methyltransferase (HMT) inhibitor SKF 91488 specifically potentia
ted the contractile responses to histamine, causing a leftward displac
ement of the concentration-response curves, whereas the diamine oxidas
e inhibitor aminoguanldine had no effect. This potentiation was attenu
ated by mechanical removal of the epithelium. The HMT activity was det
ected in the human bronchi, which was less in the epithelium-denuded t
issues than the epithelium-intact tissues. These results suggest that
HMT localized to the airway epithelium may play a protective role agai
nst histamine-mediated bronchoconstriction in humans.