Kitanaka Junichi, Kitanaka Nobue, Tsujimura Tohru, Terada Nobuyuki, Takemura Motohiko
Department of Pharmacology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan.
Eur J Pharmacol. 2002 Feb 22;437(3):179-85. doi: 10.1016/s0014-2999(02)01302-x.
The expression of mRNA for diamine oxidase (histaminase) and the enzyme activity in guinea-pig tissues were investigated. Reverse transcription-polymerase chain reaction analysis revealed that the message corresponding to the long form present in humans and rats was expressed abundantly in the small intestine and liver. Small but detectable amounts of diamine oxidase mRNA were observed in the kidney, stomach, cerebellum, thalamus+hypothalamus, and cerebral cortex. Northern blot analysis showed that the message (2.8 kb in size) was observed abundantly in the liver and small intestine and was detectable in the kidney and stomach but not in the brain or lung. In situ hybridization showed that diamine oxidase mRNA was localized throughout the liver and epithelial cells of the small intestine. Diamine oxidase activity was detected at various levels in different tissues of the guinea-pig at the following relative abundance: liver>small intestine>lung, kidney>stomach. Histamine dose-dependently induced the contraction of sections of the guinea-pig small intestine, and the pretreatment of the tissue section with aminoguanidine (100 microM), a diamine oxidase inhibitor, but not with S-[4-(N,N-dimethylamino)butyl]isothiourea (100 microM), an inhibitor of histamine N-methyltransferase, shifted the dose-response curve of histamine-induced contraction to lower concentrations. These results suggest that diamine oxidase has a crucial role in the degradation of histamine in the guinea-pig small intestine and probably in the liver.
研究了豚鼠组织中二胺氧化酶(组胺酶)的mRNA表达及酶活性。逆转录-聚合酶链反应分析显示,与人类和大鼠中存在的长形式相对应的信息在小肠和肝脏中大量表达。在肾脏、胃、小脑、丘脑+下丘脑和大脑皮层中观察到少量但可检测到的二胺氧化酶mRNA。Northern印迹分析表明,该信息(大小为2.8 kb)在肝脏和小肠中大量观察到,在肾脏和胃中可检测到,但在大脑或肺中未检测到。原位杂交显示二胺氧化酶mRNA定位于整个肝脏和小肠上皮细胞。在豚鼠的不同组织中检测到不同水平的二胺氧化酶活性,其相对丰度如下:肝脏>小肠>肺、肾脏>胃。组胺剂量依赖性地诱导豚鼠小肠切片收缩,用二胺氧化酶抑制剂氨基胍(100 microM)预处理组织切片,但不用组胺N-甲基转移酶抑制剂S-[4-(N,N-二甲基氨基)丁基]异硫脲(100 microM)预处理,可使组胺诱导收缩的剂量反应曲线向较低浓度偏移。这些结果表明,二胺氧化酶在豚鼠小肠中,可能在肝脏中,对组胺的降解起关键作用。