{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:05:37Z","timestamp":1787061937770,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T00:00:00Z","timestamp":1426032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Science Council of Taiwan","award":["NSC 102-2314-B-418-005"],"award-info":[{"award-number":["NSC 102-2314-B-418-005"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03c9-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.<\/jats:p>","DOI":"10.3390\/ijms16035555","type":"journal-article","created":{"date-parts":[[2015,3,11]],"date-time":"2015-03-11T10:50:21Z","timestamp":1426071021000},"page":"5555-5571","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Palmitoylethanolamide Inhibits Glutamate Release in Rat Cerebrocortical Nerve Terminals"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1374-5189","authenticated-orcid":false,"given":"Tzu-Yu","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-3231","authenticated-orcid":false,"given":"Cheng-Wei","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"},{"name":"Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Chan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Kuei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4675-0259","authenticated-orcid":false,"given":"Su-Jane","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Basic Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan"},{"name":"School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Distinct, New Taipei City 24205, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"55","DOI":"10.2174\/1871527311312010010","article-title":"Palmitoylethanolamide in homeostatic and traumatic central nervous system injuries","volume":"12","author":"Esposito","year":"2013","journal-title":"CNS Neurol. 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