Inhibitory effects of tetrandrine and hernandezine on Ca2+ mobilization in rat glioma C6 cells.
The effects of tetrandrine (TET), a Ca2+ antagonist of Chinese herbal origin, and hernandezine (HER), a structural analogue of TET, on Ca2+ mobilization were studied in rat glioma C6 cells. TET and HER alone did not affect the resting cytoplasmic Ca2+ concentration ([Ca2+]i). TET and HER inhibited the peak and sustained elevation of [Ca2+]i induced by bombesin and thapsigargin (TG), a microsomal Ca2+ ATPase inhibitor, in a dose-dependent manner. The doses of TET or HER needed to abolish the sustained and peak increase in [Ca2+]i induced by bombesin and TG were 30 microM and 300 microM, respectively. TET and HER did not increase inositol 1,4,5-trisphosphate (IP3) accumulation by themselves but inhibited IP3 accumulation elevated by bombesin. In permeabilized C6 cells, the addition of IP3 and TG released Ca2+ from intracellular stores. Pretreatment with TET or HER abolished Ca2+ release from intracellular stores induced by bombesin and TG. In the absence of extracellular Ca2+, the addition of 3 mM Ca2+ to extracellular medium slightly increased [Ca2+]i, which indicated Ca2+ entry due to leakage of Ca2+ at the plasma membrane but not Ca2+ influx through Ca2+ channels. TET and HER did not affect this leakage entry of Ca2+. The present results suggest that TET and HER inhibit Ca2+ release from intracellular stores as well as Ca2+ entry from extracellular medium evoked by bombesin and TG. In addition, TET and HER inhibit IP3 accumulation induced by bombesin in rat glioma C6 cells.
Imoto
K
K
Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
Takemura
H
H
Kwan
C Y
CY
Sakano
S
S
Kaneko
M
M
Ohshika
H
H
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D044182:Benzylisoquinolines; D001839:Bombesin / Q000633:toxicity; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000633:toxicity; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D051381:Rats; D019284:Thapsigargin / Q000633:toxicity; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D004365:Drugs, Chinese Herbal; D004791:Enzyme Inhibitors; C009438:tetrandrine; C067193:hernandezine; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D001839:Bombesin; D002118:Calcium