Ultrapotent effects of salvinorin A, a hallucinogenic compound from Salvia divinorum, on LPS-stimulated murine macrophages and its anti-inflammatory action in vivo
| Autor: | Kevin Lewellyn, Raffaele Capasso, Livio Luongo, Sabatino Maione, Francesca Borrelli, Gabriella Aviello, Angelo A. Izzo, Maria De Chiaro, Barbara Romano, Jordan K. Zjawiony, Francesca Guida |
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| Přispěvatelé: | Aviello, Gabriella, Borrelli, Francesca, F., Guida, Romano, Barbara, K., Lewellyn, M., De Chiaro, L., Luongo, J. K., Zjawiony, S., Maione, Izzo, ANGELO ANTONIO, Capasso, Raffaele |
| Rok vydání: | 2011 |
| Předmět: |
Lipopolysaccharides
Male Agonist medicine.drug_class medicine.medical_treatment Anti-Inflammatory Agents Nitric Oxide Synthase Type II (+)-Naloxone Pharmacology Nitric Oxide κ-opioid receptor Diterpenes Clerodane Mice chemistry.chemical_compound Receptor Cannabinoid CB1 Rimonabant Drug Discovery medicine Animals Edema Salvia Cells Cultured Genetics (clinical) Inflammation Mice Inbred ICR Salvinorin Macrophages Receptors Opioid kappa Salvinorin A chemistry Cyclooxygenase 2 Molecular Medicine lipids (amino acids peptides and proteins) Cannabinoid Inflammation Mediators Opioid antagonist medicine.drug |
| Zdroj: | Journal of Molecular Medicine. 89:891-902 |
| ISSN: | 1432-1440 0946-2716 |
| DOI: | 10.1007/s00109-011-0752-4 |
| Popis: | The hallucinogenic compound, salvinorin A, is a potent κ-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1-10 pM) reduced LPS-stimulated nitrite, TNF-α and IL-10 (but not IL-1β) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant Salvinorin A also prevented KOR and CB1 hyperexpression induced by LPS. In vivo, salvinorin A reduced the LPS- and the carrageenan-induced paw oedema and formalin-induced inflammatory pain, in a nor-binaltorphimine and rimonabant-sensitive manner. It is concluded that salvinorin A-via KORs and CB1 receptors-exerts ultrapotent actions on macrophages and also shows moderate antinflammatory effects in vivo. |
| Databáze: | OpenAIRE |
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