title: Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria.
abstract: The aim of this study was to investigate changes in the activity of individual mitochondrial respiratory chain complexes (I, II/III, IV) and citrate synthase induced by pharmacologically different cannabinoids. In vitro effects of selected cannabinoids on mitochondrial enzymes were measured in crude mitochondrial fraction isolated from pig brain. Both cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol, anandamide, and R-(+)-WIN55,212-2, and antagonist/inverse agonists of cannabinoid receptors, AM251, and cannabidiol were examined in pig brain mitochondria. Different effects of these cannabinoids on mitochondrial respiratory chain complexes and citrate synthase were found. Citrate synthase activity was decreased only by Δ(9)-tetrahydrocannabinol and AM251. Significant increase in the complex I activity was induced by anandamide. At micromolar concentration, all the tested cannabinoids inhibited the activity of electron transport chain complexes II/III and IV. Stimulatory effect of anandamide on activity of complex I may participate on distinct physiological effects of endocannabinoids compared to phytocannabinoids or synthetic cannabinoids. Common inhibitory effect of cannabinoids on activity of complex II/III and IV confirmed a non-receptor-mediated mechanism of cannabinoid action on individual components of system of oxidative phosphorylation.
authors.affiliation: Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00, Prague 2, Czech Republic.
authors.forename: Namrata
authors.initials: N
authors.lastname: Singh
authors.affiliation: Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00, Prague 2, Czech Republic. hroudova.jana@gmail.com.
authors.forename: Jana
authors.initials: J
authors.lastname: Hroudová
authors.affiliation: Department of Psychiatry, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 11, 120 00, Prague 2, Czech Republic.
authors.forename: Zdeněk
authors.initials: Z
authors.lastname: Fišar
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D042967:Electron Transport Complex I / Q000378:metabolism; D042963:Electron Transport Complex II / Q000378:metabolism; D014450:Electron Transport Complex III / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D013552:Swine
chemical_list: D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; D042963:Electron Transport Complex II; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III
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