Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) havereceived 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 3,5dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEAconcentrations 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 isresponsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and thestimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects ofendogenous 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.

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

Maccarrone M;
2008

Abstract

Of the endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG) havereceived 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 3,5dihydroxyphenylglycine (DHPG) depressed inhibitory transmission in the striatum through selective involvement of 2-AG metabolism and stimulation of presynaptic CB1 receptors. Elevation of AEAconcentrations 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 isresponsible for the downregulation of the other eCB. AEA is an endovanilloid substance, and thestimulation of transient receptor potential vanilloid 1 (TRPV1) channels mimicked the effects ofendogenous 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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11697/155724
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 253
  • ???jsp.display-item.citation.isi??? 241
social impact