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Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine.
Xenobiotica. 2016 Nov; 46(11):977-85.X

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Uehara S
a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .
Uno Y
b Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd , Kainan , Wakayama , Japan .
Inoue T
c Department of Applied Developmental Biology , Central Institute for Experimental Animals , Kawasaki , Japan , and.
Okamoto E
a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .
Sasaki E
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.
Yamazaki H
a Laboratory of Drug Metabolism and Pharmacokinetics , Showa Pharmaceutical University , Machida , Tokyo , Japan .

MeSH

AnimalsAstemizoleCytochrome P-450 CYP2J2Cytochrome P-450 Enzyme SystemHistamine H1 Antagonists, Non-SedatingHumansIntestine, SmallLiverMacaca fascicularisMiceRatsTerfenadine

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26899760

Citation

Uehara, Shotaro, et al. "Marmoset Cytochrome P450 2J2 Mainly Expressed in Small Intestines and Livers Effectively Metabolizes Human P450 2J2 Probe Substrates, Astemizole and Terfenadine." Xenobiotica; the Fate of Foreign Compounds in Biological Systems, vol. 46, no. 11, 2016, pp. 977-85.
Uehara S, Uno Y, Inoue T, et al. Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine. Xenobiotica. 2016;46(11):977-85.
Uehara, S., Uno, Y., Inoue, T., Okamoto, E., Sasaki, E., & Yamazaki, H. (2016). Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine. Xenobiotica; the Fate of Foreign Compounds in Biological Systems, 46(11), 977-85. https://doi.org/10.3109/00498254.2016.1146366
Uehara S, et al. Marmoset Cytochrome P450 2J2 Mainly Expressed in Small Intestines and Livers Effectively Metabolizes Human P450 2J2 Probe Substrates, Astemizole and Terfenadine. Xenobiotica. 2016;46(11):977-85. PubMed PMID: 26899760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Marmoset cytochrome P450 2J2 mainly expressed in small intestines and livers effectively metabolizes human P450 2J2 probe substrates, astemizole and terfenadine. AU - Uehara,Shotaro, AU - Uno,Yasuhiro, AU - Inoue,Takashi, AU - Okamoto,Eriko, AU - Sasaki,Erika, AU - Yamazaki,Hiroshi, Y1 - 2016/02/22/ PY - 2016/2/23/entrez PY - 2016/2/24/pubmed PY - 2017/2/10/medline KW - CYP2J2 KW - Common marmoset KW - cooperativity KW - drug oxidation SP - 977 EP - 85 JF - Xenobiotica; the fate of foreign compounds in biological systems JO - Xenobiotica VL - 46 IS - 11 N2 - 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. SN - 1366-5928 UR - https://www.unboundmedicine.com/medline/citation/26899760/Marmoset_cytochrome_P450_2J2_mainly_expressed_in_small_intestines_and_livers_effectively_metabolizes_human_P450_2J2_probe_substrates_astemizole_and_terfenadine_ DB - PRIME DP - Unbound Medicine ER -