Cannabinoid-induced changes in respiration of brain mitochondria
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25195527
DOI
10.1016/j.toxlet.2014.09.002
PII: S0378-4274(14)01322-8
Knihovny.cz E-resources
- Keywords
- AM251, Anandamide, Cannabidiol, Respiratory rate, WIN 55,212-2, Δ(9)-Tetrahydrocannabinol,
- MeSH
- Cannabinoid Receptor Agonists pharmacology MeSH
- Benzoxazines pharmacology MeSH
- Cell Respiration drug effects MeSH
- Endocannabinoids pharmacology MeSH
- Energy Metabolism drug effects MeSH
- Drug Inverse Agonism MeSH
- Cannabidiol pharmacology MeSH
- Cannabinoids pharmacology MeSH
- Arachidonic Acids pharmacology MeSH
- Mitochondria drug effects metabolism MeSH
- Morpholines pharmacology MeSH
- Brain drug effects metabolism MeSH
- Naphthalenes pharmacology MeSH
- Piperidines pharmacology MeSH
- Polyunsaturated Alkamides pharmacology MeSH
- Swine MeSH
- Pyrazoles pharmacology MeSH
- Receptor, Cannabinoid, CB1 drug effects metabolism MeSH
- Signal Transduction drug effects MeSH
- Dronabinol pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone MeSH Browser
- Cannabinoid Receptor Agonists MeSH
- AM 251 MeSH Browser
- anandamide MeSH Browser
- Benzoxazines MeSH
- Endocannabinoids MeSH
- Cannabidiol MeSH
- Cannabinoids MeSH
- Arachidonic Acids MeSH
- Morpholines MeSH
- Naphthalenes MeSH
- Piperidines MeSH
- Polyunsaturated Alkamides MeSH
- Pyrazoles MeSH
- Receptor, Cannabinoid, CB1 MeSH
- Dronabinol MeSH
Cannabinoids exert various biological effects that are either receptor-mediated or independent of receptor signaling. Mitochondrial effects of cannabinoids were interpreted either as non-receptor-mediated alteration of mitochondrial membranes, or as indirect consequences of activation of plasma membrane type 1 cannabinoid receptors (CB1). Recently, CB1 receptors were confirmed to be localized to the membranes of neuronal mitochondria, where their activation directly regulates respiration and energy production. Here, we performed in-depth analysis of cannabinoid-induced changes of mitochondrial respiration using both an antagonist/inverse agonist of CB1 receptors, AM251 and the cannabinoid receptor agonists, Δ(9)-tetrahydrocannabinol (THC), cannabidiol, anandamide, and WIN 55,212-2. Relationships were determined between cannabinoid concentration and respiratory rate driven by substrates of complex I, II or IV in pig brain mitochondria. Either full or partial inhibition of respiratory rate was found for the tested drugs, with an IC50 in the micromolar range, which verified the significant role of non-receptor-mediated mechanism in inhibiting mitochondrial respiration. Effect of stepwise application of THC and AM251 evidenced protective role of AM251 and corroborated the participation of CB1 receptor activation in the inhibition of mitochondrial respiration. We proposed a model, which includes both receptor- and non-receptor-mediated mechanisms of cannabinoid action on mitochondrial respiration. This model explains both the inhibitory effect of cannabinoids and the protective effect of the CB1 receptor inverse agonist.
References provided by Crossref.org
Assessment of the Effects of Drugs on Mitochondrial Respiration
