Cytochrome P-450 isozymes in metabolic activation of delta 9-tetrahydrocannabinol by rat liver microsomes.
delta 9-Tetrahydrocannabinol (THC) was incubated with a reconstituted system consisting of dilauroylphosphatidylcholine, NADPH-cytochrome c reductase, cytochrome b5, and cytochrome P-450 (P-450) isozyme UT-2, UT-4, or UT-5, which was purified from liver microsomes of adult male rats. It was biotransformed by UT-2 to 11-OH-delta 9-THC and 3'-OH-delta 9-THC, and by UT-4 to 8 beta-OH-delta 9-THC and 11-OH-delta 9-THC. UT-5, however, showed only a little activity for 11-OH-delta 9-THC formation. Activity of the isozyme UT-2 for 11-OH-delta 9-THC formation from delta 9-THC was calculated to be 4.07 nmol/min/nmol P-450 while those of UT-2 for the formations of 16 alpha-OH-testosterone (16 alpha-OH-T), 2 alpha-OH-T, and androstenedione from testosterone were 14.7, 6.6, and 2.2 nmol/min/nmol P-450, respectively. Anti-P-450 UT-2 IgG fraction obtained from rabbit serum dose-dependently suppressed formations of 16 alpha-OH-T, 2 alpha-OH-T, and androstenedione from testosterone with liver microsomes of adult male rats. The antibody, in the amount that inhibited above 90% of 16 alpha-OH-T and 2 alpha-OH-T formations from testosterone, also reduced 80% of the microsomal formations of 11-OH-delta 9-THC and 3'-OH-delta 9-THC from delta 9-THC, as compared with control experiments using preimmune IgG fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Narimatsu
S
S
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Watanabe
K
K
Matsunaga
T
T
Yamamoto
I
I
Imaoka
S
S
Funae
Y
Y
Yoshimura
H
H
D000735:Androstenedione / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism; D013759:Dronabinol / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D000906:Antibodies; D007074:Immunoglobulin G; D007527:Isoenzymes; D013739:Testosterone; D000735:Androstenedione; D013759:Dronabinol; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase