http://www.cnr.it/ontology/cnr/individuo/prodotto/ID169909

Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors (Articolo in rivista)

Type

Prodotto della ricerca (Classe)
Articolo in rivista (Classe)

Label

Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors (Articolo in rivista) (literal)

Anno

2007-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1038/sj.bjp.0707145 (literal)

Alternative label

Maione S, De Petrocellis L, de Novellis V, Schiano Moriello A, Petrosino S, Palazzo E, Rossi FS, Woodward DF, Di Marzo V. (2007)
Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors
in British journal of pharmacology; Nature Publishing Group, New York (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Maione S, De Petrocellis L, de Novellis V, Schiano Moriello A, Petrosino S, Palazzo E, Rossi FS, Woodward DF, Di Marzo V. (literal)

Pagina inizio

766 (literal)

Pagina fine

781 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

150 (literal)

Rivista

British journal of pharmacology (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

16 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

6 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

1Department of Experimental Medicine - Section of Pharmacology 'L Donatelli', Second University of Naples, Naples, Italy; 2Endocannabinoid Research Group, Institute of Cybernetics 'E Caianiello', CNR, Pozzuoli (Naples), Italy; 3Endocannabinoid Research Group, Institute of Biomolecular Chemistry, CNR, Pozzuoli (Naples), Italy; 4Department of Pharmaceutical Sciences, University of Salerno, Fisciano, Italy 5Allergan Inc., Irvine, CA, USA (literal)

Titolo

Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors (literal)

Abstract

BACKGROUND AND PURPOSE: N-arachidonoyl-serotonin (AA-5-HT) is an inhibitor of fatty acid amide hydrolase (FAAH)-catalysed hydrolysis of the endocannabinoid/ endovanilloid compound, anandamide (AEA). We investigated if AA-5-HT antagonizes the transient receptor potential vanilloid-1 (TRPV1) channel and, as FAAH and TRPV1 are targets for analgesic compounds, if it exerts analgesia in rodent models of hyperalgesia. EXPERIMENTAL APPROACH: AA-5-HT was tested in vitro, on HEK-293 cells overexpressing the human or the rat recombinant TRPV1 receptor, and in vivo, in rats and mice treated with formalin and in rats with chronic constriction injury of the sciatic nerve. The levels of the endocannabinoids, AEA and 2-arachidonoylglycerol, in supraspinal (periaqueductal grey, rostral ventromedial medulla), spinal or peripheral (skin) tissues were measured. KEY RESULTS: AA-5-HT behaved as an antagonist at both rat and human TRPV1 receptors (IC(50)=37-40 nM against 100 nM capsaicin). It exerted strong analgesic activity in all pain models used here. This activity was partly due to FAAH inhibition, elevation of AEA tissue levels and indirect activation of cannabinoid CB(1) receptors, as it was reversed by AM251, a CB(1) antagonist. AA-5-HT also appeared to act either via activation/desensitization of TRPV1, following elevation of AEA, or as a direct TRPV1 antagonist, as suggested by the fact that its effects were either reversed by capsazepine and 5'-iodo-resiniferatoxin, two TRPV1 antagonists, or mimicked by these compounds administered alone. CONCLUSIONS AND IMPLICATIONS: Possibly due to its dual activity as a FAAH inhibitor and TRPV1 antagonist, AA-5-HT was highly effective against both acute and chronic peripheral pain. (literal)

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