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Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria

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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, Δ9-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 Δ9-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.

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Acknowledgments

The study is supported by the International Post-Doc Research Fund of Charles University in Prague and by PRVOUK-P26/LF1/4 given by Charles University in Prague, Czech Republic. The authors are grateful to Mr. Zdeněk Hanuš for his technical assistance.

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The authors declare that they have no conflicts of interest concerning this article.

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Authors and Affiliations

  1. 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

    Namrata Singh, Jana Hroudová & Zdeněk Fišar

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  1. Namrata Singh
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  2. Jana Hroudová
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  3. Zdeněk Fišar
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Correspondence to Jana Hroudová.

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Singh, N., Hroudová, J. & Fišar, Z. Cannabinoid-Induced Changes in the Activity of Electron Transport Chain Complexes of Brain Mitochondria. J Mol Neurosci 56, 926–931 (2015). https://doi.org/10.1007/s12031-015-0545-2

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  • DOI: https://doi.org/10.1007/s12031-015-0545-2

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