Dataset Information

Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2.

ABSTRACT: Phytocannabinoids have well-known cardiovascular implications. For instance, ?9-tetrahydrocannabinol (?9-THC), the principal component of cannabis, induces tachycardia in humans. In order to understand the impact of phytocannabinoids on human cardiovascular health, there is a need to study the metabolism of phytocannabinoids by cardiac cytochromes p450 (CYPs). CYP2J2, the primary CYP of cardiomyocytes, is responsible for the metabolism of the endocannabinoid, anandamide (AEA), into cardioprotective epoxides (EET-EAs). Herein, we have investigated the kinetics of the direct metabolism of six phytocannabinoids (?9-THC, ?8-tetrahydrocannabinol, cannabinol, cannabidiol, cannabigerol, and cannabichromene) by CYP2J2. CYP2J2 mainly produces 1'/1?-OH metabolites of these phytocannabinoids. These phytocannabinoids are metabolized with greater catalytic efficiency compared to the metabolism of AEA by CYP2J2. We have also determined that the phytocannabinoids are potent inhibitors of CYP2J2-mediated AEA metabolism, with ?9-THC being the strongest inhibitor. Most of the inhibition of CYP2J2 by the phytocannabinoids follow a noncompetitive inhibition model, and therefore dramatically reduce the formation of EET-EAs by CYP2J2. Taken together, these data demonstrate that phytocannabinoids are directly metabolized by CYP2J2 and inhibit human cardiac CYP2J2, leading to a reduction in the formation of cardioprotective EET-EAs.

SUBMITTER: Arnold WR

PROVIDER: S-EPMC5964033 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2.

Arnold William R WR Weigle Austin T AT Das Aditi A

Journal of inorganic biochemistry 20180407

Phytocannabinoids have well-known cardiovascular implications. For instance, Δ9-tetrahydrocannabinol (Δ9-THC), the principal component of cannabis, induces tachycardia in humans. In order to understand the impact of phytocannabinoids on human cardiovascular health, there is a need to study the metabolism of phytocannabinoids by cardiac cytochromes p450 (CYPs). CYP2J2, the primary CYP of cardiomyocytes, is responsible for the metabolism of the endocannabinoid, anandamide (AEA), into cardioprotect ...[more]

PMID: 29689453

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Dataset Information

Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2.

Publications

Cross-talk of cannabinoid and endocannabinoid metabolism is mediated via human cardiac CYP2J2.

Similar Datasets

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