Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation

S. Narimatsu, Y. Masubuchi, S. Hosokawa, S. Ohmori, M. Kitada, T. Suzuki

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The oxidative metabolism of bunitrolol, an adrenergic β-receptor antagonist was examined in human liver microsomes fortified with an NADPH- generating system. The microsomal fractions (n=11) showed bunitrolol 4- hydroxylase activities, which correlated well with CYP2D6 contents (correlation coefficient, r=0.854), dehrisoquine 4-hydroxylase (r=0.953) and imipramine 2-hydroxylase (r=0.976) activities. On the other hand, the bunitrolol 4-hydroxylase activity showed relatively poor correlations with CYP3A4 content (r=0.552) and testosterone 6β-hydroxylase activity (r=0.668). The bunitrolol 4-hydroxylase activity was significantly inhibited by quinidine, a selective inhibitor for CYP2D6. Polyclonal antibodies raised against rat liver microsomal cytochrome P450BTL, which is thought to belong to the CYP2D subfamily, effectively inhibited bunitrolol 4-hydroxylation. In contrast, polyclonal antibodies raised against human liver microsomal CYP3A4 did not show any inhibitory effect on the activity. These results suggest that CYP2D6 is involved in the bunitrolol 4-hydroxylase activity in human liver microsomes.

Original languageEnglish
Pages (from-to)803-807
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume17
Issue number6
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Cytochromes
Hydroxylation
Cytochrome P-450 CYP2D6
Cytochrome P-450 CYP3A
Liver
Liver Microsomes
Mixed Function Oxygenases
Adrenergic Antagonists
Quinidine
Antibodies
NADP
Human Activities
Testosterone
bunitrolol
bunitrolol 4-hydroxylase

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Narimatsu, S., Masubuchi, Y., Hosokawa, S., Ohmori, S., Kitada, M., & Suzuki, T. (1994). Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation. Biological and Pharmaceutical Bulletin, 17(6), 803-807.

Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation. / Narimatsu, S.; Masubuchi, Y.; Hosokawa, S.; Ohmori, S.; Kitada, M.; Suzuki, T.

In: Biological and Pharmaceutical Bulletin, Vol. 17, No. 6, 1994, p. 803-807.

Research output: Contribution to journalArticle

Narimatsu, S, Masubuchi, Y, Hosokawa, S, Ohmori, S, Kitada, M & Suzuki, T 1994, 'Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation', Biological and Pharmaceutical Bulletin, vol. 17, no. 6, pp. 803-807.
Narimatsu S, Masubuchi Y, Hosokawa S, Ohmori S, Kitada M, Suzuki T. Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation. Biological and Pharmaceutical Bulletin. 1994;17(6):803-807.
Narimatsu, S. ; Masubuchi, Y. ; Hosokawa, S. ; Ohmori, S. ; Kitada, M. ; Suzuki, T. / Involvement of a cytochrome P4502D subfamily in human liver microsomal bunitrolol 4-hydroxylation. In: Biological and Pharmaceutical Bulletin. 1994 ; Vol. 17, No. 6. pp. 803-807.
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