Sasaki Takamitsu, Masubuchi Akiko, Yamamura Mayumi, Watanabe Nobuaki, Hiratsuka Masahiro, Mizugaki Michinao, Itoh Kunio, Tanaka Yorihisa
Department of Biopharmaceutics, Tohoku Pharmaceutical University, Sendai, Japan.
Biopharm Drug Dispos. 2006 Jul;27(5):247-55. doi: 10.1002/bdd.504.
Aldehyde oxidase catalysed 2-oxidation activity of the (S)-enantiomer of RS-8359, a selective and reversible monoamine oxidase A (MAO-A) inhibitor, was investigated in liver cytosolic fractions from ten rat strains. Remarkably large strain differences were observed with approximately a 230 variation between the highest activity in the Wistar-Imamichi strain and the lowest activity in the Slc:Wistar strain. The activities of Crj:SD and Slc:SD strain rats were considerably low, and that of the F344/DuCrj strain was very low. Among six Wistar strains, Crj:Wistar, Slc:Wistar, WKY/Izm, WKAH/Hkm, Jcl:Wistar and Wistar-Imamichi, the Slc:Wistar strain rats showed exceptionally low 2-oxidation activity that was comparable to that of the F344/DuCrj strain. The rat strain differences in the catalytic activity of aldehyde oxidase could correlate in part with the expressed levels of protein based on the mRNA of aldehyde oxidase. However, no small discrepancy existed in the almost negligible catalytic activity and the fairly high expression levels of protein and mRNA in the F344/DuCrj and Slc:Wistar strain rats. Some genetic factors might possibly be one of reasons for the discrepancy.
在来自十个大鼠品系的肝脏胞质组分中，研究了醛氧化酶对选择性可逆单胺氧化酶A（MAO-A）抑制剂RS-8359的（S）-对映体的2-氧化活性。观察到显著的品系差异，Wistar-Imamichi品系的最高活性与Slc:Wistar品系的最低活性之间相差约230倍。Crj:SD和Slc:SD品系大鼠的活性相当低，而F344/DuCrj品系的活性非常低。在六个Wistar品系，即Crj:Wistar、Slc:Wistar、WKY/Izm、WKAH/Hkm、Jcl:Wistar和Wistar-Imamichi中，Slc:Wistar品系大鼠的2-氧化活性异常低，与F344/DuCrj品系相当。醛氧化酶催化活性的大鼠品系差异可能部分与基于醛氧化酶mRNA的蛋白质表达水平相关。然而，在F344/DuCrj和Slc:Wistar品系大鼠中，几乎可忽略不计的催化活性与相当高的蛋白质和mRNA表达水平之间存在一些小的差异。一些遗传因素可能是造成这种差异的原因之一。
