Effects of bifemelane on the calcium level and ATP release of the human origin astrocyte clonal cell

Abstract

The effect of bifemelane hydrochloride (bifemelane) was examined on human origin astrocyte clonal cells (Kings-1). Bifemelane (125-1000 μM) induced a dose-dependent increase in the intracellular calcium concentration ([Ca 2+]i). In the highest concentration (1000 μM), the drug caused the second large increase in [Ca2+]i during the washing. The increase that occurred during the administration partially remained in the Ca2+-free medium and was blocked by 2-aminoethoxydiphenyl borate (2-APB), an IP3-receptor blocker, indicating that the source of Ca2+ for the increase could be ascribed to the intracellular store. The increase in [Ca2+]i was not observed during washing with Ca2+-free medium, but was observed when the washing was performed with Ca2+-containing medium. Bifemelane caused a dose-dependent ATP release, but histamine and carbachol, which induced a large increase in [Ca2+]i, had no effects on the ATP release. The effects on the [Ca2+]i were blocked by pretreatment with pyridoxal phosphate-6-azophenyl-2′,4′ disulfonic acid, a P2-receptor antagonist. Although the mechanisms of ATP release induced by the drug have not been elucidated yet, the present results demonstrate that the increase in [Ca2+]i induced by bifemelane is not due to its direct effect on the cells, but is dependent upon the ATP released from the cells. ©2006 The Japanese Pharmacological Society.