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Int J Mol Sci. 2015 Mar 11;16(3):5555-71. doi: 10.3390/ijms16035555.

Palmitoylethanolamide inhibits glutamate release in rat cerebrocortical nerve terminals.

Author information

1
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. drlin1971@gmail.com.
2
Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan. drlin1971@gmail.com.
3
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. drluchengwei@gmail.com.
4
Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan. drluchengwei@gmail.com.
5
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. chiachanc@yahoo.com.tw.
6
Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. nskh9450n@yahoo.com.tw.
7
Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan. med0003@mail.fju.edu.tw.
8
School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan. med0003@mail.fju.edu.tw.

Abstract

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 Ca²⁺-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 Ca²⁺ concentration, and not due to a change in synaptosomal membrane potential. The glutamate release-inhibiting effect of PEA was prevented by the Ca(v)2.1 (P/Q-type) channel blocker ω-agatoxin IVA or the protein kinase A inhibitor H89, not affected by the intracellular Ca²⁺ 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 Ca²⁺ influx mediated by Ca(v)2.1 (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.

PMID:
25768340
PMCID:
PMC4394492
DOI:
10.3390/ijms16035555
[Indexed for MEDLINE]
Free PMC Article

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