Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine.
Histamine N-methyltransferase controls the contractile response of guinea pig trachea to histamine.
复制标题
组胺 N-甲基转移酶控制豚鼠气管对组胺的收缩反应。
DOI：
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发表时间：
1992
影响因子：
3.5
通讯作者：
H. Sasaki
中科院分区：
文献类型：
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作者：
T. Ohrui;K. Yamauchi;K. Sekizawa;Y. Ohkawara;K. Maeyama;M. Sasaki;M. Takemura;H. Wada;T. Watanabe;H. Sasaki
组胺N-甲基转移酶抑制剂SKF-91488可增强组胺对豚鼠离体气管条的收缩反应，而二胺氧化酶抑制剂氨基胍则无此作用。SKF 91488对组胺的浓度-效应曲线呈浓度依赖性地向低浓度方向移动，最大值为1个对数单位。气管具有显著的HMT活性(45.4+/-5.0pmol/min/mg蛋白)。原位杂交检测HMT mRNA显示，HMT mRNA存在于上皮细胞和内皮细胞中，以内皮细胞中表达更为丰富。去除上皮使组胺的量效曲线向低浓度移动0.8log单位，而SKF 91488仅使剥离上皮的组织的组胺量效曲线轻微移位。这些发现表明，HMT调节豚鼠气管对组胺的收缩反应，去除上皮引起的支气管对组胺的高反应性在很大程度上是由于上皮中HMT的丢失所致。
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.