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Molecular Pharmacology

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Abstract

Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily.

L M Bornheim and M A Correia
Molecular Pharmacology August 1991, 40 (2) 228-234;
L M Bornheim
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M A Correia
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Abstract

Acute cannabidiol treatment of mice inactivated hepatic microsomal cytochrome P-450IIIA (P-450IIIA) and markedly inhibited in vitro cannabinoid metabolism. Antibodies raised against purified P-450IIIA inhibited the microsomal formation of quantitatively minor cannabinoid metabolites but had no effect on the major metabolites. Cannabinoid hydroxylation to the major metabolites was used as a functional probe to isolate and purify a P-450 (termed P-450THC) from hepatic microsomes of untreated mice. The purified protein had an apparent molecular weight of 47,000 and a specific content of 15.4 nmol/mg and exhibited an absorbance maximum at 452 nm for the reduced carbon monoxide complex. NH2-terminal sequence analysis of the first 16 residues of P-450THC suggests that it is a member of the P-450IIC subfamily, because its sequence is 85 and 69% identical to published sequences of rat hepatic P-450IIC7 and P-450IIC6, respectively. P-450THC exhibited high activity for cannabinoid hydroxylation and specifically produced 6 alpha- and 7-hydroxy-delta 1-tetrahydrocannabinol, as well as 6 alpha-, 7-, and 4"-hydroxycannabidiol. Unlike anti-P-450IIIA antibody, antibody raised against purified P-450THC markedly inhibited the microsomal formation of all major cannabinoid metabolites. Similar immunoinhibition studies also revealed the existence of orthologs of mouse P-450THC and P-450IIIA in human liver microsomes. Thus, cannabidiol treatment of mice resulted in the inactivation of at least two constitutive P-450 isozymes, which together account for the majority of the detected cannabinoid metabolites.

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Molecular Pharmacology
Vol. 40, Issue 2
1 Aug 1991
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Abstract

Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily.

L M Bornheim and M A Correia
Molecular Pharmacology August 1, 1991, 40 (2) 228-234;

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Abstract

Purification and characterization of the major hepatic cannabinoid hydroxylase in the mouse: a possible member of the cytochrome P-450IIC subfamily.

L M Bornheim and M A Correia
Molecular Pharmacology August 1, 1991, 40 (2) 228-234;
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