Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes.

Masuhiro Nishimura, Akiko Koeda, Yasuyuki Suganuma, Emako Suzuki, Takefumi Shimizu, Mitsuo Nakayama, Tetsuo Satoh, Shizuo Narimatsu, Shinsaku Naito

Research output: Contribution to journalArticle

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Abstract

This study was conducted to investigate the effects of treatment with the prototypical inducers rifampicin (Rif), dexamethasone (Dex), and omeprazole (Ome) on the mRNA levels of drug-metabolizing enzymes in primary cultures of cryopreserved human, cynomolgus monkey, and rat hepatocytes. Analysis was performed by quantitative real-time RT-PCR using primers and TaqMan probes. Treatment with Ome substantially increased the mRNA levels of both CYP1A1 and CYP1A2 in human hepatocytes, but increased only the mRNA level of CYP1A1 in monkey hepatocytes, whereas it had no marked effect on the mRNA levels of CYP1A1 or CYP1A2 in rat hepatocytes. Treatment with Rif or Dex did not markedly affect the mRNA level of CYP1A in any of the hepatocyte cultures under the conditions used. All three inducers increased the mRNA level of CYP3A8 in monkey hepatocytes (in the order Rif>Dex>or=Ome), and a similar profile was observed for the mRNA level of CYP3A4 in human hepatocytes, but the potency of induction was markedly attenuated. In contrast, only Dex substantially increased the mRNA level of CYP3A1 in rat hepatocytes, with Rif and Ome showing no effects. These results indicate that the molecular mechanisms responsible for the regulation of CYP1A2 genes differ between humans and cynomolgus monkeys, although the regulatory mechanisms for CYP1A1 and CYP3A genes are similar.

Original languageEnglish
Pages (from-to)178-186
Number of pages9
JournalDrug Metabolism and Pharmacokinetics
Volume22
Issue number3
DOIs
Publication statusPublished - Jun 2007
Externally publishedYes

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Cytochrome P-450 CYP3A
Macaca fascicularis
Hepatocytes
Messenger RNA
Cytochrome P-450 CYP1A1
Omeprazole
Rifampin
Cytochrome P-450 CYP1A2
Dexamethasone
Haplorhini
Genes
Real-Time Polymerase Chain Reaction
Enzymes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes. / Nishimura, Masuhiro; Koeda, Akiko; Suganuma, Yasuyuki; Suzuki, Emako; Shimizu, Takefumi; Nakayama, Mitsuo; Satoh, Tetsuo; Narimatsu, Shizuo; Naito, Shinsaku.

In: Drug Metabolism and Pharmacokinetics, Vol. 22, No. 3, 06.2007, p. 178-186.

Research output: Contribution to journalArticle

Nishimura, M, Koeda, A, Suganuma, Y, Suzuki, E, Shimizu, T, Nakayama, M, Satoh, T, Narimatsu, S & Naito, S 2007, 'Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes.', Drug Metabolism and Pharmacokinetics, vol. 22, no. 3, pp. 178-186. https://doi.org/10.2133/dmpk.22.178
Nishimura, Masuhiro ; Koeda, Akiko ; Suganuma, Yasuyuki ; Suzuki, Emako ; Shimizu, Takefumi ; Nakayama, Mitsuo ; Satoh, Tetsuo ; Narimatsu, Shizuo ; Naito, Shinsaku. / Comparison of inducibility of CYP1A and CYP3A mRNAs by prototypical inducers in primary cultures of human, cynomolgus monkey, and rat hepatocytes. In: Drug Metabolism and Pharmacokinetics. 2007 ; Vol. 22, No. 3. pp. 178-186.
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