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Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals
The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca(2+)-dependent release of glutamate, which was triggered by exposing synapt...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394492/ https://www.ncbi.nlm.nih.gov/pubmed/25768340 http://dx.doi.org/10.3390/ijms16035555 |
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author | Lin, Tzu-Yu Lu, Cheng-Wei Wu, Chia-Chan Huang, Shu-Kuei Wang, Su-Jane |
author_facet | Lin, Tzu-Yu Lu, Cheng-Wei Wu, Chia-Chan Huang, Shu-Kuei Wang, Su-Jane |
author_sort | Lin, Tzu-Yu |
collection | PubMed |
description | The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca(2+)-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca(2+) concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type) channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca(2+) release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca(2+) influx mediated by Cav2.1 (P/Q-type) channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway. |
format | Online Article Text |
id | pubmed-4394492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-43944922015-05-21 Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals Lin, Tzu-Yu Lu, Cheng-Wei Wu, Chia-Chan Huang, Shu-Kuei Wang, Su-Jane Int J Mol Sci Article The effect of palmitoylethanolamide (PEA), an endogenous fatty acid amide displaying neuroprotective actions, on glutamate release from rat cerebrocortical nerve terminals (synaptosomes) was investigated. PEA inhibited the Ca(2+)-dependent release of glutamate, which was triggered by exposing synaptosomes to the potassium channel blocker 4-aminopyridine. This release inhibition was concentration dependent, associated with a reduction in cytosolic Ca(2+) concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Cav2.1 (P/Q-type) channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca(2+) release inhibitors dantrolene and CGP37157, and partially antagonized by the cannabinoid CB1 receptor antagonist AM281. Based on these results, we suggest that PEA exerts its presynaptic inhibition, likely through a reduction in the Ca(2+) influx mediated by Cav2.1 (P/Q-type) channels, thereby inhibiting the release of glutamate from rat cortical nerve terminals. This release inhibition might be linked to the activation of presynaptic cannabinoid CB1 receptors and the suppression of the protein kinase A pathway. MDPI 2015-03-11 /pmc/articles/PMC4394492/ /pubmed/25768340 http://dx.doi.org/10.3390/ijms16035555 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lin, Tzu-Yu Lu, Cheng-Wei Wu, Chia-Chan Huang, Shu-Kuei Wang, Su-Jane Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title | Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title_full | Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title_fullStr | Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title_full_unstemmed | Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title_short | Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals |
title_sort | palmitoylethanolamide inhibits glutamate release in rat cerebrocortical nerve terminals |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394492/ https://www.ncbi.nlm.nih.gov/pubmed/25768340 http://dx.doi.org/10.3390/ijms16035555 |
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