Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine
Ohrui, T.; Yamauchi, K.; Sekizawa, K.; Ohkawara, Y.; Maeyama, K.; Sasaki, M.; Takemura, M.; Wada, H.; Watanabe, T.; Sasaki, H.
Journal of Pharmacology and Experimental Therapeutics 261(3): 1268-1272
1992
ISSN/ISBN: 0022-3565 PMID: 1534842 Document Number: 388754
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.