Obata Toshio, Aomine Masahiro
Res Commun Mol Pathol Pharmacol. 2009;122-123:13-26.
The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.
本研究基于抑制剂敏感性考察了猴血小板单胺氧化酶(MAO)的性质。猴血小板以β-苯乙胺(β-PEA)为底物时表现出较高的MAO活性,以5-羟色胺(5-HT)为底物时A-型MAO活性极低。此外,猴血小板MAO对作为B-型MAO抑制剂的司来吉兰敏感,而以β-PEA作为B-型MAO底物时,对作为A-型MAO抑制剂的氯吉兰和哈马灵不太敏感。猴血小板中的B-型MAO在55℃热处理下比脑中的B-型MAO更稳定。在37℃用胰蛋白酶消化4小时后,发现血小板中的MAO以β-PEA为底物时比脑中的MAO被抑制约70%。三环类抗抑郁药丙咪嗪和去甲替林抑制B-型MAO活性的效力比脑中的B-型MAO更强。然而,当使用非环类抗抑郁药诺米芬辛时,猴血小板B-型MAO活性受到的抑制作用较弱。所有这些试剂都是猴血小板中B-型MAO的非竞争性抑制剂。本研究表明,猴血小板MAO是单一的B-型MAO,且对三环类抗抑郁药敏感。