HISTAMINE N-METHYLTRANSFERASE MODULATES HUMAN BRONCHIAL SMOOTH-MUSCLECONTRACTION

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.