Uehara Shotaro, Uno Yasuhiro, Inoue Takashi, Sasaki Erika, Yamazaki Hiroshi
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
J Vet Med Sci. 2017 Feb 4;79(2):267-272. doi: 10.1292/jvms.16-0459. Epub 2016 Nov 26.
Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of endogenous catechol amines and estrogens and exogenous catechol-type of drugs. A Parkinson's disease model of common marmoset (Callithrix jacchus) has been widely used in preclinical studies to evaluate inhibitory potential of new drug candidates on marmoset COMT. Despite COMT inhibitors could potentiate the pharmacological action of levodopa on Parkinson's disease in animal models, marmoset COMT cDNA has not yet been identified and characterized. In this study, a cDNA highly homologous to human COMT was cloned from marmoset livers. This cDNA encoded 268 amino acids containing a transmembrane region and critical amino acid residues for catalytic function. The amino acid sequences of marmoset COMT shared high sequence identity (90%) with human COMT. COMT mRNA was expressed in all five tissues tested, including brain, lung, liver, kidney and small intestine, and was more abundant in marmoset liver and kidney. Membrane-bound COMT was immunochemically detected in livers and kidneys, whereas soluble COMT was detected in livers, similar to humans. These results indicated that the molecular characteristics of marmoset COMT were generally similar to the human ortholog.
儿茶酚-O-甲基转移酶（COMT）催化内源性儿茶酚胺和雌激素以及外源性儿茶酚类药物的O-甲基化反应。普通狨猴（Callithrix jacchus）的帕金森病模型已广泛用于临床前研究，以评估新药候选物对狨猴COMT的抑制潜力。尽管在动物模型中COMT抑制剂可增强左旋多巴对帕金森病的药理作用，但狨猴COMT cDNA尚未得到鉴定和表征。在本研究中，从狨猴肝脏中克隆出了与人COMT高度同源的cDNA。该cDNA编码268个氨基酸，包含一个跨膜区域和催化功能的关键氨基酸残基。狨猴COMT的氨基酸序列与人COMT具有高度的序列同一性（90%）。COMT mRNA在所检测的所有五个组织中均有表达，包括脑、肺、肝、肾和小肠，且在狨猴肝脏和肾脏中表达更为丰富。在肝脏和肾脏中通过免疫化学方法检测到了膜结合型COMT，而在肝脏中检测到了可溶性COMT，这与人类情况相似。这些结果表明，狨猴COMT的分子特征与人类直系同源物总体相似。
