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Effect of FS11052, an Inhibitor of Exocytosis, on Neurite Extension in Rat Hippocampal Neurons and PC12 Cells

신경전달물질 방출 저해제 FS11052가 신경세포와 PC12 세포의 돌기신장에 미치는 영향

  • Lee Yun-Sik (Department of Pharmacology, College of Medicine & Institute of Biomedical Science, Hanyang University) ;
  • Kim Dong-Seob (School of Applied and Life Science, College of Natural Resource and Life Sciences, Pusan Nagtional University)
  • 이윤식 (한양대학교 의과대학 약리학교실) ;
  • 김동섭 (부산대학교 생명자원과학대학 생명응용과학부)
  • Published : 2006.04.01

Abstract

FS11052, a novel microbial metabolite from Streptomyces spp. was identified as a small molecular substance and shown inhibition activities for the release of neurotransmitter from rat hippocampal neuron and PC12 cells. FS11052 is an inhibitor of tritiated norepinephrine ($[^3H]-NE$) release in high $K^+$ buffer solution containing ionomycin, indicating that FS11052 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. When examined the effect of FS11052 on glucuronidase release from guinea pig neutrophils, FS11052 inhibited glucuronidase release: when treated with $5{\mu}g/ml$ of FS11052, which was not induced cellular cytotoxicity. The fact that the glucuronidase release in neutrophil and norepinephrine release in neuron was inhibited suggests the similarity in the locations and the mechanisms of FS11052 action targets. When treated with $5{\mu}g/ml$ of FS11052, $[^3H]-NE$ release and neurite extension for both rat hippocampal neurons and PC12 cells were prevented. These observations of FS11052 functioning as an inhibitor of neurotransmitter release suggest that FS11052 has an important role in synaptic transmission in neuron.

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