A novel effect of bifemelane, a nootropic drug, on intracellular Ca2+ levels in rat cerebral astrocytes.
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 microM, bifemelane induced a slow onset and small increase in the [Ca2+]i, while at higher concentrations (100 - 300 microM), 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.
School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
Yoshitoku
Y
Yoshida
Akira
A
Nakane
Mitsuhiro
M
Morita
Yoshihisa
Y
Kudo
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D004305:Dose-Response Relationship, Drug; D018697:Nootropic Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
D001559:Benzhydryl Compounds; D018697:Nootropic Agents; D019284:Thapsigargin; D002118:Calcium; C031906:bifemelane