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KMID : 1140120060110010022
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Cancer Prevention Research
2006 Volume.11 No. 1 p.22 ~ p.29
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Screening of Low Molecular Metabolite, S8877 as an Inhibitor of Neurotransmitter Release from PC12 Cells
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Lee Yun-Sik
Jhee Ok-Hwa
Kang Ju-Seop
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Abstract
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We established an in vitro experimental system using the following procedure. We first introduced tritium-labeled norepinephrine ([3H]-NE) into PC12 cells. The [3H]-NE incorporated into PC12 cells were then stimulated by a high concentration (60 mM) of K buffer during 12 minutes. Then, we collected 100μl supernatant and counted the amount of [3H]-NE release from PC12 cells with a scintillation counter. After screening fungal, Streptomyces spp. or bacterial product using this experimental system, we obtained S8877 from Streptomyces spp. which inhibited [3H]-NE release from PC12 cells. S8877 also inhibits the release of ATP as a neurotransmitter of PC12 cells and rat cortical neurons. The inhibitory effect was seen even when the PC12 cells were treated with low K buffer containing ionomycin (1μM) as an ionophore. This result suggests that the inhibitory action of S8877 on neurotransmitter release appeared after the influx of Ca2 .
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KEYWORD
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PC12 cells, Neurotransmitter release, Exocytosis, Streptomyces spp., Inhibitor
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