The anti-inflammatory mediator palmitoylethanolamide enhances the levels of 2-arachidonoyl-glycerol and potentiates its actions at TRPV1 cation channels.
Br J Pharmacol
; 173(7): 1154-62, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-25598150
ABSTRACT
BACKGROUND AND PURPOSE:
Palmitoylethanolamide (PEA) is an endogenous congener of anandamide and potentiates its actions at cannabinoid CB1 and CB2 receptors, and at transient receptor potential vanilloid type-1 (TRPV1) channels. The other endocannabinoid, 2-arachidonoylglycerol (2-AG), was recently suggested to act as a TRPV1 channel agonist. We investigated if PEA enhanced levels of 2-AGâ in vitro or in vivo and 2-AG activity at TRPV1 channels. EXPERIMENTALAPPROACH:
Endogenous lipid levels were measured by LC-MS in (i) human keratinocytes incubated with PEA (10-20 µM, 40 min, 6 and 24 h, 37°C); (ii) the blood of spontaneously Ascaris suum hypersensitive beagle dogs given a single oral dose of ultramicronized PEA (30 mg·kg(-1), 1, 2, 4 and 8 h from administration); (iii) the blood of healthy volunteers given a single oral dose of micronized PEA (300 mg, 2, 4 and 6 h from administration). Effects of 2-AG at TRPV1 channels were assessed by measuring intracellular Ca(2+) in HEK-293 cells over-expressing human TRPV1 channels. KEYRESULTS:
PEA elevated 2-AG levels in keratinocytes (â¼3-fold) and in human and canine plasma (â¼2 and â¼20-fold respectively). 2-AG dose-dependently raised intracellular Ca(2+) in HEK-293-TRPV1 cells in a TRPV1-dependent manner and desensitized the cells to capsaicin. PEA only slightly enhanced 2-AG activation of TRPV1 channels, but significantly increased 2-AG-induced TRPV1 desensitization to capsaicin (IC50 from 0.75 ± 0.04 to 0.45 ± 0.02 µM, with PEA 2 µM). CONCLUSIONS AND IMPLICATIONS These observations may explain why several effects of PEA are attenuated by cannabinoid receptor or TRPV1 channel antagonists. LINKED ARTICLES This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http//onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Palmíticos
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Anti-Inflamatórios não Esteroides
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Ácidos Araquidônicos
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Endocanabinoides
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Etanolaminas
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Canais de Cátion TRPV
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Glicerídeos
Limite:
Adolescent
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Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article