Bibliographic Details
| Title: |
Anandamide inhibits metabolism and physiological actions of 2-arachidonoylglycerol in the striatum. |
| Authors: |
Maccarrone, Mauro, Rossi, Silvia, Bari, Monica, De Chiara, Valentina, Fezza, Filomena, Musella, Alessandra, Gasperi, Valeria, Prosperetti, Chiara, Bernardi, Giorgio, Finazzi-Agrò, Alessandro, Cravatt, Benjamin F., Centonze, Diego |
| Source: |
Nature Neuroscience. Feb2008, Vol. 11 Issue 2, p152-159. 8p. 7 Graphs. |
| Subjects: |
Glutamic acid, Presynaptic receptors, Laboratory mice, Pharmacology, TRP channels, Genetics |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Psychology and Behavioral Sciences Collection |
