{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:37:16Z","timestamp":1745469436465,"version":"3.40.4"},"reference-count":26,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2011,1,1]],"date-time":"2011-01-01T00:00:00Z","timestamp":1293840000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2011]]},"abstract":"<i>Aim:<\/i> The present study was aimed at investigating the effect of <i>trans<\/i>-6-(4-chlorobutyl)-5-hydroxy-4-(phenylthio)-1-tosyl-5,6-dihydropyridine-2(1H)-one (HTDP-2), a novel synthetic compound, on the release of endogenous glutamate in rat cerebrocortical nerve terminals (synaptosomes) and exploring the possible mechanism. <i>Methods:<\/i> The release of glutamate was evoked by the K<sup>+<\/sup> channel blocker 4-aminopyridine (4-AP) and measured by an on-line enzyme-coupled fluorimetric assay. We also used a membrane potential-sensitive dye to assay nerve terminal excitability and depolarization, and a Ca<sup>2+<\/sup> indicator, Fura-2-acetoxymethyl ester, to monitor cytosolic Ca<sup>2+<\/sup> concentrations ([Ca<sup>2+<\/sup>]<sub>c<\/sub>). <i>Results:<\/i> HTDP-2 inhibited the release of glutamate evoked by 4-AP in a concentration-dependent manner. Inhibition of glutamate release by HTDP-2 was prevented by the chelating intraterminal Ca<sup>2+<\/sup> ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor <i>D<\/i><i>L<\/i>-threo-\u03b2-benzyloxyaspartate. HTDP-2 did not alter the resting synaptosomal membrane potential or 4-AP-mediated depolarization whereas it decreased the 4-AP-induced increase in [Ca<sup>2+<\/sup>]<sub>c<\/sub>. Furthermore, the inhibitory effect of HTDP-2 on the evoked glutamate release was abolished by the N-, and P\/Q-type Ca<sup>2+<\/sup> channel blocker \u03c9-conotoxin MVIIC, but not by the ryanodine receptor blocker dantrolene, or the mitochondrial Na<sup>+<\/sup>\/Ca<sup>2+<\/sup> exchanger blocker CGP37157. <i>Conclusion:<\/i> Based on these results, we suggest that, in rat cerebrocortical nerve terminals, HTDP-2 decreases voltage-dependent Ca<sup>2+<\/sup> channel activity and, in so doing, inhibits the evoked glutamate release.<\/jats:p>","DOI":"10.1159\/000328774","type":"journal-article","created":{"date-parts":[[2011,7,1]],"date-time":"2011-07-01T08:25:20Z","timestamp":1309508720000},"page":"26-32","source":"Crossref","is-referenced-by-count":1,"title":["HTDP-2, a New Synthetic Compound, Inhibits Glutamate Release through Reduction of Voltage-Dependent Ca<sup>2+<\/sup> Influx in Rat Cerebral Cortex Nerve Terminals"],"prefix":"10.1159","volume":"88","author":[{"given":"Tzu-Yu","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Kuei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang-Shing 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