Biol. Pharm. Bull., 29(12),2362-2366, December 2006

Regular Articles

Substrate Selectivity of Monoamine Oxidase A, Monoamine Oxidase B, Diamine Oxidase, and Semicarbazide-Sensitive Amine Oxidase in COS-1 Expression Systems

Yoshinori OCHIAI,^a Kunio ITOH,^a Eiichi SAKURAI,^b Mayuko ADACHI,^a and Yorihisa TANAKA^*,a

^a Department of Drug Metabolism and Pharmacokinetics, Tohoku Pharmaceutical University; 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan: and ^bAomori University; 2-3-1 Kobata, Aomori 030-0943, Japan. * To whom correspondence should be addressed. e-mail: ytanaka@tohoku-pharm.ac.jp

The substrate selectivity of monoamine oxidase A (MAO-A), monoamine oxidase B (MAO-B), diamine oxidase (DAO), and semicarbazide-sensitive amine oxidase (SSAO) was investigated in the absence of chemical inhibitors using the COS-1 cells expressed with respective amine oxidase. Serotonin (5-hydroxytryptamine), 1-methylhistamine, and histamine were preferentially oxidized by MAO-A, SSAO, and DAO, respectively, at a low substrate concentration. In contrast, benzylamine, tyramine, and β-phenylethylamine served as substrates for all of MAO-A, MAO-B, and SSAO. Each amine oxidase showed broad substrate selectivity at a high substrate concentration. The cross-inhibition was remarkable in MAO-A and MAO-B, especially in MAO-A, but not in SSAO and DAO. A study of the substrate selectivity of amine oxidases should include consideration of the effects of substrate concentration and specific chemical inhibitors.

Key words substrate selectivity; COS-1; monoamine oxidase (MAO)-A; MAO-B; diamine oxidase (DAO); semicarbazide-sensitive amine oxidase (SSAO)