title: Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.
abstract: 1. Common marmoset (Callithrix jacchus), a New World Monkey, has potential to be a useful animal model in preclinical studies. However, drug metabolizing properties have not been fully understood due to insufficient information on cytochrome P450 (P450), major drug metabolizing enzymes. 2. Marmoset P450 2J2 cDNA was isolated from marmoset livers. The deduced amino acid sequence showed a high-sequence identity (91%) with cynomolgus monkey and human P450 2J2 enzymes. A phylogenetic tree revealed that marmoset P450 2J2 was evolutionarily closer to cynomolgus monkey and human P450 2J2 enzymes, than P450 2J forms in pigs, rabbits, rats or mice. 3. Marmoset P450 2J2 mRNA was abundantly expressed in the small intestine and liver, and to a lesser extent in the brain, lung and kidney. Immunoblot analysis also showed expression of marmoset P450 2J2 protein in the small intestine and liver. 4. Enzyme assays using marmoset P450 2J2 protein heterologously expressed in Escherichia coli indicated that marmoset P450 2J2 effectively catalyzed astemizole O-demethylation and terfenadine t-butyl hydroxylation, similar to human and cynomolgus monkey P450 2J2 enzymes. 5. These results suggest the functional characteristics of P450 2J2 enzymes are similar among marmosets, cynomolgus monkeys and humans.
authors.affiliation: a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .
authors.forename: Shotaro
authors.initials: S
authors.lastname: Uehara
authors.affiliation: b Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd , Kainan , Wakayama , Japan .
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Uno
authors.affiliation: c Department of Applied Developmental Biology , Central Institute for Experimental Animals , Kawasaki , Japan , and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .
authors.forename: Eriko
authors.initials: E
authors.lastname: Okamoto
authors.affiliation: c Department of Applied Developmental Biology , Central Institute for Experimental Animals , Kawasaki , Japan , and.|d Keio Advanced Research Center, Keio University , Minato-Ku, Tokyo , Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Sasaki
authors.affiliation: a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yamazaki
mesh_terms: D000818:Animals; D016589:Astemizole / Q000378:metabolism*; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000378:metabolism*; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008252:Macaca fascicularis / Q000378:metabolism*; D051379:Mice; D051381:Rats; D016593:Terfenadine / Q000378:metabolism*
chemical_list: C000717350:CYP2J2 protein, human; D039563:Histamine H1 Antagonists, Non-Sedating; D016593:Terfenadine; D016589:Astemizole; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2
keywords: CYP2J2; Common marmoset; cooperativity; drug oxidation