In:
The FASEB Journal, Wiley, Vol. 22, No. S1 ( 2008-03)
Abstract:
Δ 9 ‐Tetrahydrocannabinol (Δ 9 ‐THC) is the primary psychoactive compound found in cannabis plants which invoke physiological responses via cannabinoid CB1 receptors. THC derivatives are known to be the subject of cytochrome P450 (P450) and UDP‐glucuronosyltransferases (UGTs) metabolism. Despite ample P450 characterization data, there remain gaps in our understanding of human phase II enzymes responsible for THC derivative metabolism and excretion. The activities of 12 human recombinant UGTs towards several THC derivatives, cannabinol (CBN), cannabidiol (CBD), (−) ‐Δ 8 ‐THC, (−) ‐Δ 9 ‐THC, (±)‐11‐hydroxy‐Δ 9 ‐THC (11‐OH‐THC), and (−)‐11‐nor‐9‐carboxy‐Δ 9 ‐THC (COOH‐THC), have been investigated in this study. C14‐labeling assays and HPLC‐MS/MS product confirmations show that UGT1A1, −1A3, −1A8, −1A9, −1A10, and −2B7 are involved in the glucuronidation of CBN, CBD, 11‐OH‐THC, and COOH‐THC. CBN and 11‐OH‐THC are primarily metabolized by an extrahepatic isoform, UGT1A10, with apparent K m values of 55 and 16 μM, respectively. COOH‐THC is a substrate for 2 hepatic UGTs, −1A1 and −1A3. All of the tested enzymes show little to no activity with (−) ‐Δ 8 ‐THC and (−)‐Δ 9 ‐THC. This is the first demonstration that cannabinoids are glucuronidated by specific human recombinant UGTs, with UGT1A10 and 1A3 being the major isoforms involved. (NIH‐DK60109 and GM075893 to AR‐P; U90/CCU616974‐07 to JM)
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fasebj.22.1_supplement.711.4
Language:
English
Publisher:
Wiley
Publication Date:
2008
detail.hit.zdb_id:
1468876-1
detail.hit.zdb_id:
639186-2
SSG:
12
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