Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals

International Journal of Molecular Sciences

Tzu-Yu Lin¹  Cheng-Wei Lu¹  Chia-Chan Wu¹  Shu-Kuei Huang¹  Su-Jane Wang² 

[1] Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan; E-Mails:;Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan

关键词: PEA;    glutamate release;    cerebrocortical nerve terminals;    voltage-dependent Ca²⁺ channels;    cannabinoid CB1 receptors;    protein kinase A;   

DOI  :  10.3390/ijms16035555

来源: mdpi

【 摘 要 】

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 Cav2.1 (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 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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.