| The stimulation of ketogenesis by cannabinoids in cultured astrocytes defines carnitine palmitoyltransferase I as a new ceramide-activated enzyme. | |
MedLine Citation:
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PMID: 10098887 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The effects of cannabinoids on ketogenesis in primary cultures of rat astrocytes were studied. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, produced a malonyl-CoA-independent stimulation of carnitine palmitoyltransferase I (CPT-I) and ketogenesis from [14C]palmitate. The THC-induced stimulation of ketogenesis was mimicked by the synthetic cannabinoid HU-210 and was prevented by pertussis toxin and the CB1 cannabinoid receptor antagonist SR141716. Experiments performed with different cellular modulators indicated that the THC-induced stimulation of ketogenesis was independent of cyclic AMP, Ca2+, protein kinase C, and mitogen-activated protein kinase (MAPK). The possible involvement of ceramide in the activation of ketogenesis by cannabinoids was subsequently studied. THC produced a CB1 receptor-dependent stimulation of sphingomyelin breakdown that was concomitant to an elevation of intracellular ceramide levels. Addition of exogenous sphingomyelinase to the astrocyte culture medium led to a MAPK-independent activation of ketogenesis that was quantitatively similar and not additive to that exerted by THC. Furthermore, ceramide activated CPT-I in astrocyte mitochondria. Results thus indicate that cannabinoids stimulate ketogenesis in astrocytes by a mechanism that may rely on CB1 receptor activation, sphingomyelin hydrolysis, and ceramide-mediated activation of CPT-I. |
Authors:
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C Blázquez; C Sánchez; A Daza; I Galve-Roperh; M Guzmán |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of neurochemistry Volume: 72 ISSN: 0022-3042 ISO Abbreviation: J. Neurochem. Publication Date: 1999 Apr |
Date Detail:
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Created Date: 1999-04-13 Completed Date: 1999-04-13 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1759-68 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / cytology, drug effects, enzymology* Calcium / metabolism Calcium-Calmodulin-Dependent Protein Kinases / metabolism Carnitine O-Palmitoyltransferase / metabolism* Cells, Cultured Cerebral Cortex / cytology Cyclic AMP / metabolism Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Ketone Bodies / metabolism* Malonyl Coenzyme A / metabolism Mitochondria / enzymology Piperidines / pharmacology Protein Kinase C / metabolism Psychotropic Drugs / pharmacology* Pyrazoles / pharmacology Rats Receptors, Cannabinoid Receptors, Drug / metabolism Sphingomyelin Phosphodiesterase / pharmacology Sphingomyelins / metabolism* Sphingosine / analogs & derivatives, pharmacology Tetrahydrocannabinol / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Ketone Bodies; 0/N-acetylsphingosine; 0/Piperidines; 0/Psychotropic Drugs; 0/Pyrazoles; 0/Receptors, Cannabinoid; 0/Receptors, Drug; 0/Sphingomyelins; 123-78-4/Sphingosine; 158681-13-1/rimonabant; 1972-08-3/Tetrahydrocannabinol; 524-14-1/Malonyl Coenzyme A; 60-92-4/Cyclic AMP; 7440-70-2/Calcium; EC 2.3.1.21/Carnitine O-Palmitoyltransferase; EC 2.7.11.13/Protein Kinase C; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases; EC 3.1.4.12/Sphingomyelin Phosphodiesterase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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