HISTAMINE N-METHYLTRANSFERASE CONTROLS THE CONTRACTILE RESPONSE OF GUINEA-PIG TRACHEA TO HISTAMINE

被引:0
|
作者
OHRUI, T
YAMAUCHI, K
SEKIZAWA, K
OHKAWARA, Y
MAEYAMA, K
SASAKI, M
TAKEMURA, M
WADA, H
WATANABE, T
SASAKI, H
TAKISHIMA, T
机构
[1] TOHOKU UNIV,SCH MED,DEPT INTERNAL MED 1,SENDAI,MIYAGI 980,JAPAN
[2] TOHOKU UNIV,SCH MED,DEPT PHARMACOL,SENDAI,MIYAGI 980,JAPAN
[3] OSAKA UNIV,SCH MED,DEPT PHARMACOL 2,OSAKA,JAPAN
来源
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS | 1992年 / 261卷 / 03期
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中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
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页码:1268 / 1272
页数:5
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