Obata T, Egashira T, Yamanaka Y
Department of Pharmacology, Medical College of Oita, Japan.
Res Commun Chem Pathol Pharmacol. 1989 Oct;66(1):69-85.
Amine oxidase activity in plasma of rats were investigated after pretreatment with the perilobular hepatotoxin allyl formate (AF). Amine oxidase activities in plasma elevated after administration of AF 0.1 ml/kg i.p. to male rats with 1 microM and 100 microM benzylamine (Bz), 10 microM beta-phenylethylamine (beta-PEA) and 100 microM serotonin (5-HT) as substrates. But the complete inhibition of amine oxidase activities with 5-HT and beta-PEA were not observed by clorgyline as A-form MAO inhibitor and deprenyl as beta-form MAO inhibitor. The deamination of 1 microM Bz was not inhibited at high concentrations of these MAO inhibitors, while it was inhibited at low concentrations of phenelzine and semicarbazide. On the other hand, the deamination of 100 microM Bz was highly sensitive with these MAO inhibitors, while it was less sensitive with phenelzine and semicarbazide as compared with 1 microM Bz. Then, the Km values of amine oxidase in plasma of AF-administered rats with Bz as substrate were determined from Lineweaver-Burk double reciprocal plots. Two Km values for Bz of high and low Bz concentration in amine oxidase in plasma of AF-administered rats were obtained. However, this Km value of low Bz concentration was not obtained from liver mitochondria and microsomes of control rat and AF-administered rats. The Km value for beta-PEA of MAO in plasma of AF-administered rats was the same as the values of rat liver mitochondrial MAO. These results indicate that native mitochondrial MAO was released from the liver, and two or more distinct amine oxidases were released from other organs in response to AF.
在用小叶周围肝毒素甲酸烯丙酯(AF)预处理后,研究了大鼠血浆中的胺氧化酶活性。以1 microM和100 microM苄胺(Bz)、10 microMβ-苯乙胺(β-PEA)和100 microM血清素(5-HT)为底物,给雄性大鼠腹腔注射0.1 ml/kg AF后,血浆中的胺氧化酶活性升高。但是,作为A-型单胺氧化酶抑制剂的氯吉兰和作为β-型单胺氧化酶抑制剂的司来吉兰并未完全抑制5-HT和β-PEA的胺氧化酶活性。在这些单胺氧化酶抑制剂的高浓度下,1 microM Bz的脱氨基作用未被抑制,而在苯乙肼和氨基脲的低浓度下则被抑制。另一方面,100 microM Bz的脱氨基作用对这些单胺氧化酶抑制剂高度敏感,而与1 microM Bz相比,对苯乙肼和氨基脲的敏感性较低。然后,根据Lineweaver-Burk双倒数图确定以Bz为底物的AF给药大鼠血浆中胺氧化酶的Km值。获得了AF给药大鼠血浆中胺氧化酶中高、低Bz浓度的两个Bz的Km值。然而,对照大鼠和AF给药大鼠的肝线粒体和微粒体未获得低Bz浓度的该Km值。AF给药大鼠血浆中MAO对β-PEA的Km值与大鼠肝线粒体MAO的值相同。这些结果表明,天然线粒体MAO从肝脏释放,并且响应于AF,从其他器官释放了两种或更多种不同的胺氧化酶。