Cannabinoid-induced changes in respiration of brain mitochondria
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25195527
DOI
10.1016/j.toxlet.2014.09.002
PII: S0378-4274(14)01322-8
Knihovny.cz E-zdroje
- Klíčová slova
- AM251, Anandamide, Cannabidiol, Respiratory rate, WIN 55,212-2, Δ(9)-Tetrahydrocannabinol,
- MeSH
- agonisté kanabinoidních receptorů farmakologie MeSH
- benzoxaziny farmakologie MeSH
- buněčné dýchání účinky léků MeSH
- endokanabinoidy farmakologie MeSH
- energetický metabolismus účinky léků MeSH
- inverzní agonismus léků MeSH
- kanabidiol farmakologie MeSH
- kanabinoidy farmakologie MeSH
- kyseliny arachidonové farmakologie MeSH
- mitochondrie účinky léků metabolismus MeSH
- morfoliny farmakologie MeSH
- mozek účinky léků metabolismus MeSH
- naftaleny farmakologie MeSH
- piperidiny farmakologie MeSH
- polynenasycené alkamidy farmakologie MeSH
- prasata MeSH
- pyrazoly farmakologie MeSH
- receptor kanabinoidní CB1 účinky léků metabolismus MeSH
- signální transdukce účinky léků MeSH
- tetrahydrokanabinol farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone MeSH Prohlížeč
- agonisté kanabinoidních receptorů MeSH
- AM 251 MeSH Prohlížeč
- anandamide MeSH Prohlížeč
- benzoxaziny MeSH
- endokanabinoidy MeSH
- kanabidiol MeSH
- kanabinoidy MeSH
- kyseliny arachidonové MeSH
- morfoliny MeSH
- naftaleny MeSH
- piperidiny MeSH
- polynenasycené alkamidy MeSH
- pyrazoly MeSH
- receptor kanabinoidní CB1 MeSH
- tetrahydrokanabinol 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.
Citace poskytuje Crossref.org
Assessment of the Effects of Drugs on Mitochondrial Respiration
