A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca2+ Levels in Rat Cerebral Astrocytes

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  • Yoshida Yoshitoku
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
  • Nakane Akira
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
  • Morita Mitsuhiro
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan
  • Kudo Yoshihisa
    School of Life Science, Tokyo University of Pharmacy and Life Science, Japan

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  • A Novel Effect of Bifemelane, a Nootropic Drug, on Intracellular Ca〔2+〕 Levels in Rat Cerebral Astrocytes
  • Novel Effect of Bifemelane a Nootropic Drug on Intracellular Ca 2 Levels in Rat Cerebral Astrocytes

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Abstract

We investigated the effects of bifemelane, a nootropic drug, on the intracellular calcium concentration ([Ca2+]i) in rat cerebral astrocytes using a Ca2+ imaging device. At concentrations of 10 – 30 μM, bifemelane induced a slow onset and small increase in the [Ca2+]i, while at higher concentrations (100 – 300 μM), it induced a rapid transient increase in the [Ca2+]i during administration and a second large increase was seen during drug washout. The first peak was observed in Ca2+-free medium, but its onset was significantly delayed, and no second peak was seen. Neither of these effects was seen in cells treated with thapsigargin, a specific inhibitor of endoplasmic reticulum Ca2+-ATPase, in Ca2+-free medium. When thapsigargin-treated astrocytes were returned to normal medium containing Ca2+ (1.8 mM), the [Ca2+]i increased significantly, and this effect was reversely inhibited by bifemelane. We conclude that bifemelane causes the first peak by stimulating release from intracellular Ca2+ stores and the second by capacitive entry through store–operated Ca2+ channels. Although the detail mechanisms of action of the drug are still unknown, bifemelane will be provided as a pharmacological tool for basic studies on astrocytes.<br>

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