Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors
| Autor: | MAIONE, Sabatino, DE PETROCELLIS L, DE NOVELLIS, Vito, MORIELLO AS, PETROSINO S, PALAZZO, E, ROSSI FS, WOODWARD DF, DI MARZO V., PALAZZO, Enza |
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| Přispěvatelé: | Maione, Sabatino, DE PETROCELLIS, L, DE NOVELLIS, Vito, Moriello, A, Petrosino, S, Palazzo, E, Rossi, F, Woodward, Df, DI MARZO, V., Palazzo, Enza |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Serotonin Injections Subcutaneous TRPV Cation Channels Arachidonic Acids Palmitic Acids Amidohydrolases Cell Line Mice Receptor Cannabinoid CB1 Cannabinoid Receptor Modulators Animals FAAH pain Enzyme Inhibitors Rats Wistar Pain Measurement endocannabinoid Analgesics Non-Narcotic cannabinoid Amides Research Papers Recombinant Proteins Rats nervous system Ethanolamines vanilloid lipids (amino acids peptides and proteins) psychological phenomena and processes Endocannabinoids |
| Zdroj: | British journal of pharmacology 150 (2007): 766–781. doi:10.1038/sj.bjp.0707145 info:cnr-pdr/source/autori:Maione S, De Petrocellis L, de Novellis V, Schiano Moriello A, Petrosino S, Palazzo E, Rossi FS, Woodward DF, Di Marzo V./titolo:Analgesic actions of N-arachidonoyl-serotonin, a fatty acid amide hydrolase inhibitor with antagonistic activity at vanilloid TRPV1 receptors/doi:10.1038%2Fsj.bjp.0707145/rivista:British journal of pharmacology/anno:2007/pagina_da:766/pagina_a:781/intervallo_pagine:766–781/volume:150 |
| DOI: | 10.1038/sj.bjp.0707145 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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