Stimulation of Noradrenaline Release by T-588, a Cognitive Enhancer, in PC12 Cells

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Author(s)

Abstract

Previously, we reported that(R)−(−)−1−(benzo[b]thiophen−5−yl)−2−[2−(N, N−diethylamino)ethoxy]ethanol hydrochloride(T−588), a novel putative cognitive enhancer, stimulated noradrenaline(NA)release from rat cerebral cortical slices.In this study, we investigated the effects of T−588 compared to other secretagogues on NA release from PC12 cells.Addition of as little as 10 μM T−588 stimulated [<SUP>3</SUP>H]NA release in a dose−dependent and an extracellular Ca<SUP>2+</SUP>−independent manner from PC12 cells.Ten micromolar ionomycin−, 300 μM adenosine−5′−O−(γ−thiotriphosphate)− and 10 μM forskolin−induced extracellular Ca<SUP>2+</SUP>−dependent [<SUP>3</SUP>H]−NA release was further enhanced by 30 μM T−588.Cytosolic synaptophysin and 25−kDa synaptosome−associated protein immunoreactivity was increased by addition of T−588 in a dose−dependent manner.Interestingly, increases in synaptic vesicle−related proteins triggered by T−588 had a 4−min lag time and were completely dependent on extracellular CaCl<SUB>2</SUB>.These findings suggest that T−588 stimulates NA release from PC12 cells in a Ca<SUP>2+</SUP>−independent manner.T−588 also induced the translocation of synaptic vesicles in a Ca<SUP>2+</SUP>−dependent manner.

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 82(1), 59-66, 2000-01-01

    The Japanese Pharmacological Society

References:  41

Codes

  • NII Article ID (NAID)
    10008182708
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    00215198
  • NDL Article ID
    4966481
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  NDL  J-STAGE 
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