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Abstract

Catalytic and immunologic similarities between monkey and human liver cytochrome P-450db1 (human cytochrome P-450 2D6).

S V Otton, R F Tyndale, D Wu, T Inaba, W Kalow and E M Sellers
Drug Metabolism and Disposition January 1992, 20 (1) 1-5;
S V Otton
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R F Tyndale
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D Wu
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T Inaba
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W Kalow
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E M Sellers
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Abstract

In vivo pharmacogenetic studies have suggested that the monkey may be an animal model for the human polymorphism of cytochrome P-450 2D6 (also called cytochrome P-450db1). In the present study, the catalytic, immunologic, and electrophoretic properties of cytochrome P-450db1 in liver microsomes from African green monkeys (Cercopithecus aethiops) were examined and compared with P-450db1 in human liver microsomes. Using sparteine as the substrate, the activity of microsomal P-450db1 from the two sources was indistinguishable in terms of the pattern of sparteine metabolites produced, the apparent Ki values of 8 competitive inhibitors (r = 0.94, p less than 0.001), and the extent of immunoinhibition by anti-rat P-450db1 antibody. Kinetic analyses demonstrated that the apparent KM values of the high affinity component of sparteine oxidation in monkey liver microsomes fell within the range observed in human livers; the Vmax of this component was as much as six times greater than the highest value reported for human liver. Western immunoblots showed a protein band in monkey liver microsomes that co-migrated with P-450db1 in human liver. The high degree of similarity observed here between P-450db1 of monkey and human liver microsomes suggests that the monkey will be a good animal model for P-450db1 enzyme studies, and possibly for studies of the role of this enzyme in drug abuse and dependence.

 

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Drug Metabolism and Disposition
Vol. 20, Issue 1
1 Jan 1992
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Abstract

Catalytic and immunologic similarities between monkey and human liver cytochrome P-450db1 (human cytochrome P-450 2D6).

S V Otton, R F Tyndale, D Wu, T Inaba, W Kalow and E M Sellers
Drug Metabolism and Disposition January 1, 1992, 20 (1) 1-5;

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Abstract

Catalytic and immunologic similarities between monkey and human liver cytochrome P-450db1 (human cytochrome P-450 2D6).

S V Otton, R F Tyndale, D Wu, T Inaba, W Kalow and E M Sellers
Drug Metabolism and Disposition January 1, 1992, 20 (1) 1-5;
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