title: 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 - 1,000 microM) induced a dose-dependent increase in the intracellular calcium concentration ([Ca(2+)](i)). In the highest concentration (1,000 microM), the drug caused the second large increase in [Ca(2+)](i) during the washing. The increase that occurred during the administration partially remained in the Ca(2+)-free medium and was blocked by 2-aminoethoxydiphenyl borate (2-APB), an IP(3)-receptor blocker, indicating that the source of Ca(2+) for the increase could be ascribed to the intracellular store. The increase in [Ca(2+)](i) was not observed during washing with Ca(2+)-free medium, but was observed when the washing was performed with Ca(2+)-containing medium. Bifemelane caused a dose-dependent ATP release, but histamine and carbachol, which induced a large increase in [Ca(2+)](i), had no effects on the ATP release. The effects on the [Ca(2+)](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 [Ca(2+)](i) induced by bifemelane is not due to its direct effect on the cells, but is dependent upon the ATP released from the cells.
authors.affiliation: School of Life Science, Tokyo University of Pharmacy and Life Science, Japan.
authors.forename: Yoshitoku
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Haruno
authors.initials: H
authors.lastname: Kumagai
authors.forename: Yoshiumi
authors.initials: Y
authors.lastname: Ohkubo
authors.forename: Remi
authors.initials: R
authors.lastname: Tsuchiya
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Morita
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Miyakawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kudo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001896:Boron Compounds / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D018679:Cholinergic Agonists / Q000494:pharmacology; D002999:Clone Cells; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000378:metabolism; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018697:Nootropic Agents / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001896:Boron Compounds; D015220:Calcium Channels; D018679:Cholinergic Agonists; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018697:Nootropic Agents; D058919:Purinergic P2 Receptor Antagonists; D018160:Receptors, Cytoplasmic and Nuclear; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D006632:Histamine; D000255:Adenosine Triphosphate; D002217:Carbachol; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium; C031906:bifemelane