Cloning and expression of a novel catechol-<i>O</i>-methyltransferase in common marmosets
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- UEHARA Shotaro
- Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
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- UNO Yasuhiro
- Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Wakayama, Japan
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- INOUE Takashi
- Department of Applied Developmental Biology, Central Institute for Experimental Animals, Kawasaki, Japan
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- SASAKI Erika
- Department of Applied Developmental Biology, Central Institute for Experimental Animals, Kawasaki, Japan Keio Advanced Research Center, Keio University, Minato-ku, Tokyo, Japan
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- YAMAZAKI Hiroshi
- Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan
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Abstract
<p>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.</p>
Journal
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- Journal of Veterinary Medical Science
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Journal of Veterinary Medical Science 79 (2), 267-272, 2017
JAPANESE SOCIETY OF VETERINARY SCIENCE