Effects of bifemelane on the calcium level and ATP release of the human origin astrocyte clonal cell.
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.
Yoshida
Yoshitoku
Y
School of Life Science, Tokyo University of Pharmacy and Life Science, Japan.
Kumagai
Haruno
H
Ohkubo
Yoshiumi
Y
Tsuchiya
Remi
R
Morita
Mitsuhiro
M
Miyakawa
Hiroyoshi
H
Kudo
Yoshihisa
Y
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
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