Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have received the most study. A functional interaction between these molecules has never been described. Using mouse brain slices, we found that stimulation of metabotropic glutamate 5 receptors by 3,5-dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEA concentrations by pharmacological or genetic inhibition of AEA degradation reduced the levels, metabolism and physiological effects of 2-AG. Exogenous AEA and the stable AEA analog methanandamide inhibited basal and DHPG-stimulated 2-AG production, confirming that AEA is responsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and the stimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects of endogenous AEA on 2-AG metabolism through a previously unknown glutathione-dependent pathway. Consistently, the interaction between AEA and 2-AG was lost after pharmacological and genetic inactivation of TRPV1 channels.

Maccarrone, M., Rossi, S., Bari, M., De Chiara, V., Fezza, F., Musella, A., et al. (2008). Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. NATURE NEUROSCIENCE, 11(2), 152-159 [10.1038/nn2042].

Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum

FEZZA, FILOMENA;GASPERI, VALERIA;BERNARDI, GIORGIO;CENTONZE, DIEGO
2008-01-01

Abstract

Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have received the most study. A functional interaction between these molecules has never been described. Using mouse brain slices, we found that stimulation of metabotropic glutamate 5 receptors by 3,5-dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEA concentrations by pharmacological or genetic inhibition of AEA degradation reduced the levels, metabolism and physiological effects of 2-AG. Exogenous AEA and the stable AEA analog methanandamide inhibited basal and DHPG-stimulated 2-AG production, confirming that AEA is responsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and the stimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects of endogenous AEA on 2-AG metabolism through a previously unknown glutathione-dependent pathway. Consistently, the interaction between AEA and 2-AG was lost after pharmacological and genetic inactivation of TRPV1 channels.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/10
Settore MED/26 - Neurologia
English
Con Impact Factor ISI
2 arachidonoylglycerol; 3,5 dihydroxyphenylglycine; 4 aminobutyric acid; anandamide; cannabinoid 1 receptor; fatty acid amidase; glutathione; metabotropic receptor 5; methanandamide; vanilloid receptor 1; animal tissue; article; brain metabolism; brain slice; cholesterol metabolism; controlled study; corpus striatum; down regulation; mouse; nonhuman; presynaptic nerve; priority journal; stimulation; synaptic transmission; upregulation; Amidohydrolases; Animals; Arachidonic Acids; Corpus Striatum; Down-Regulation; Drug Interactions; Endocannabinoids; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; gamma-Aminobutyric Acid; Glutathione; Glycerides; Methoxyhydroxyphenylglycol; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Patch-Clamp Techniques; Polyunsaturated Alkamides; Protein Binding; Receptor, Cannabinoid, CB1; Synaptic Transmission; Time Factors; TRPV Cation Channels
Maccarrone, M., Rossi, S., Bari, M., De Chiara, V., Fezza, F., Musella, A., et al. (2008). Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. NATURE NEUROSCIENCE, 11(2), 152-159 [10.1038/nn2042].
Maccarrone, M; Rossi, S; Bari, M; De Chiara, V; Fezza, F; Musella, A; Gasperi, V; Prosperetti, C; Bernardi, G; Finazzi Agro', A; Cravatt, B; Centonze, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/28115
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