Tissue-Specific mRNA Expression Profiles of Drug-Metabolizing Enzymes and Transporters in the Cynomolgus Monkey

• Published in: DRUG METABOLISM AND PHARMACOKINETICS Vol. 24; no. 2; pp. 139 - 144
• Main Authors: Nishimura, Masuhiro, Koeda, Akiko, Morikawa, Hiroshi, Satoh, Tetsuo, Narimatsu, Shizuo, Naito, Shinsaku
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2009; Japanese Society for the Study of Xenobiotics
• Subjects: Animals; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; Cells, Cultured; cynomolgus monkey; Cytochrome P-450 CYP3A - metabolism; DNA Probes; Dose-Response Relationship, Drug; drug-metabolizing enzymes; Gene Expression; Gene Expression Profiling; Glutathione Transferase - genetics; Glutathione Transferase - metabolism; Inactivation, Metabolic; Macaca fascicularis; Male; Membrane Transport Proteins - metabolism; Microsomes, Liver - enzymology; mRNA expression; quantification; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Species Specificity; Tissue Distribution; cynomolgus monkey; quantification; drug-metabolizing enzymes; mRNA expression; tissue distribution
• ISSN: 1347-4367; 1880-0920
• DOI: 10.2133/dmpk.24.139

Pairs of forward and reverse primers and TaqMan probes specific to each of 19 drug-metabolizing enzymes (cytochrome P450s, UDP-glucuronosyltransferases, glutathione S-transferases, and sulfotransferases) and 5 transporters (ABC and SLC transporters) in the cynomolgus monkey were prepared. The expression level of each target mRNA was analyzed in total RNA obtained from three specimens of various cynomolgus monkey tissues (adrenal gland, brain, heart, kidney, large intestine, liver, lung, pancreas, prostate, small intestine, spleen, testis, and thymus) by real-time reverse transcription PCR using an Applied Biosystems 7500 Fast Real-Time PCR System. The data obtained in the present study provide useful information on tissue-specific profiles of the expression of these target mRNAs in the cynomolgus monkey, and the results are expected to be valuable in establishing drug metabolism- and transporter-mediated screening systems using the cynomolgus monkey for the evaluation of new chemical entities in new drug development.