In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 23, No. 10 ( 2003-05-15), p. 4127-4133
Abstract:
Type 1 vanilloid receptors (VR 1 ) 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 VR 1 , and AEA has been shown to afford protection against ouabain-induced in vivo excitotoxicity, in a manner that is only in part dependent on the type 1 cannabinoid (CB 1 ) receptor. In the present study, we assessed whether VR 1 is involved in neuroprotection by AEA and by arvanil, a hydrolysis-stable AEA analog that is a ligand for both VR 1 and CB 1 . 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 CB 1 receptor-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 VR 1 , as tested using arvanil, the VR 1 agonist capsaicin, and the antagonist capsazepine, leads to neuroprotective effects in this model, and arvanil is a potent neuroprotectant, acting at both CB 1 and VR 1 ; and (4) the in vivo neuroprotective effects of AEA are mediated by CB 1 but not by lipoxygenase metabolites or VR 1 .
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.23-10-04127.2003
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2003
detail.hit.zdb_id:
1475274-8
SSG:
12
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