title: The endocannabinoid 2-arachidonoylglicerol decreases calcium induced cytochrome c release from liver mitochondria.
abstract: 2-Arachidonoylglicerol (2-AG) is an endocannabinoid that mimics the pharmacological effects of Δ⁹ tetrahydrocannabinol, the psychoactive component of the plant Cannabis sativa. It is present in many mammalian tissues, such as brain, liver, spleen, heart and kidney, where it exerts different biological effects either receptor mediated or independently of receptor activation. This work analyzes the effects of 2-AG on liver mitochondrial functions. It is shown that 2-AG causes a relevant decrease of calcium induced cyclosporine A sensitive cytochrome c release from mitochondria, a process representing an early event of the apoptotic program. Cyclosporin sensitive matrix swelling and ROS production measured under the same conditions are, on the contrary, almost unaffected or even enhanced, respectively, by 2-AG. Furthemore, 2-AG is found to stimulate resting state succinate oxidase activity and to inhibit oligomycin sensitive F₀F₁ ATP synthase activity. All these effects are apparently associated with 2-AG dependent alteration in the fluidity of the mitochondrial membranes, which was measured as generalized polarization of laurdan fluorescence.
authors.affiliation: Department of Basic Medical Sciences, University of Bari, Policlinico, Piazza G. Cesare, 70124 Bari, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Zaccagnino
authors.forename: Susanna
authors.initials: S
authors.lastname: D'Oria
authors.forename: Luigi Luciano
authors.initials: LL
authors.lastname: Romano
authors.forename: Almerinda
authors.initials: A
authors.lastname: Di Venere
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
authors.forename: Michele
authors.initials: M
authors.lastname: Lorusso
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism*; D063388:Endocannabinoids; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D007166:Immunosuppressive Agents; D017382:Reactive Oxygen Species; D016572:Cyclosporine; D045304:Cytochromes c; D002118:Calcium