Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: Role of vanilloid receptors and lipoxygenases
| Autor: | Mauro Maccarrone, Filomena Fezza, Gerrit A. Veldink, Johannes F.G. Vliegenthart, Wouter B. Veldhuis, M. van der Stelt, G. van Zadelhoff, Klaas Nicolay, Mayken W. Wadman, Peter R. Bär, V. Di Marzo |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Agonist Cannabinoid receptor Polyunsaturated Alkamides medicine.drug_class Receptors Drug medicine.medical_treatment Metabolite Lipoxygenase Arachidonic Acids Pharmacology Neuroprotection arvanil chemistry.chemical_compound Cannabinoid Receptor Modulators medicine Animals Masoprocol anandamide Rats Wistar Brain Chemistry Brain Mapping Blood Cells Cannabinoids General Neuroscience ouabain neurodegeneration Brain Anandamide cannabinoid Endocannabinoid system Rats Neuroprotective Agents Animals Newborn chemistry Ethanolamines vanilloid Nerve Degeneration Fatty Acids Unsaturated neuroprotection lipids (amino acids peptides and proteins) Cannabinoid Capsaicin CNS Capsazepine excitotoxicity Endocannabinoids Cellular/Molecular |
| Zdroj: | Europe PubMed Central Journal of Neuroscience, 23(10), 4127-4133 Scopus-Elsevier 23 (2003): 4127–4133. info:cnr-pdr/source/autori:Veldhuis WB, van der Stelt M, Wadman MW, van Zadelhoff G, Maccarrone M, Fezza F, Veldink GA, Vliegenthart JF, Bar PR, Nicolay K, Di Marzo V./titolo:Neuroprotection by the endogenous cannabinoid anandamide and arvanil against in vivo excitotoxicity in the rat: role of vanilloid receptors and lipoxygenases./doi:/rivista:/anno:2003/pagina_da:4127/pagina_a:4133/intervallo_pagine:4127–4133/volume:23 |
| Popis: | Type 1 vanilloid receptors (VR1) have been identified recently in the brain, in which they serve as yet primarily undetermined purposes. The endocannabinoid anandamide (AEA) and some of its oxidative metabolites are ligands for VR1, and AEA has been shown to afford protection against ouabain-inducedin vivoexcitotoxicity, in a manner that is only in part dependent on the type 1 cannabinoid (CB1) receptor. In the present study, we assessed whether VR1is involved in neuroprotection by AEA and by arvanil, a hydrolysis-stable AEA analog that is a ligand for both VR1and CB1. Furthermore, we assessed the putative involvement of lipoxygenase metabolites of AEA in conveying neuroprotection. Using HPLC and gas chromatography/mass spectroscopy, we demonstrated that rat brain and blood cells converted AEA into 12-hydroxy-N-arachidoylethanolamine (12-HAEA) and 15-hydroxy-N-arachidonoylethanolamine (15-HAEA) and that this conversion was blocked by addition of the lipoxygenase inhibitor nordihydroguaiaretic acid. Using magnetic resonance imaging we show the following: (1) pretreatment with the reduced 12-lipoxygenase metabolite of AEA, 12-HAEA, attenuated cytotoxic edema formation in a CB1receptor-independent manner in the acute phase after intracranial injection of the Na+/K+-ATPase inhibitor ouabain; (2) the reduced 15-lipoxygenase metabolite, 15-HAEA, enhanced the neuroprotective effect of AEA in the acute phase; (3) modulation of VR1, as tested using arvanil, the VR1agonist capsaicin, and the antagonist capsazepine, leads to neuroprotective effects in this model, and arvanil is a potent neuroprotectant, acting at both CB1and VR1; and (4) thein vivoneuroprotective effects of AEA are mediated by CB1but not by lipoxygenase metabolites or VR1. |
| Databáze: | OpenAIRE |
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