Calcium antagonistic actions of tetrandrine depend on cell types.
We examined the effects of tetrandrine (TET) on Ca2+ mobilization in various types of cells using inositol trisphosphate-generating drugs and compared it with those using the microsomal Ca(2+)-ATPase inhibitor thapsigargin (TG) which is a tool for analyzing Ca2+ store-regulated Ca2+ entry (capacitative Ca2+ entry). In rat pheochromocytoma PC12 cells, 100 microM TET abolished high K+ (30 mM)-induced sustained increase in [Ca2+]i and partially inhibited bradykinin (1 microM)-induced or TG (100 nM)-induced Ca2+ entry. In NIH/3T3 fibroblasts, 100 microM TET abolished Ca2+ entry induced by bombesin (1 microM) or TG (100 nM). In rat glioma C6 cells, the addition of 100 microM TET reduced the sustained elevation of [Ca2+]i induced by endothelin 1 (10 nM) or TG (100 nM) declining to the resting level. In rat parotid acinar cells, 100 microM TET abolished a sustained increase in [Ca2+]i induced by carbachol (100 microM) or TG (100 nM). In human leukemia T-cell line Jurkat, 100 microM TET did not inhibit Ca2+ entry evoked by the anti-CD3 antibody OKT3 (10 micrograms/ml) or TG (100 nM). The present results suggest that the action of TET on Ca2+ entry is dependent on cell types.
Takemura
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Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
Kwan
C Y
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Ohshika
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D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D001920:Bradykinin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007293:Inosine Triphosphate / Q000096:biosynthesis; D016716:PC12 Cells; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D013729:Terpenes; D007293:Inosine Triphosphate; C009438:tetrandrine; D019284:Thapsigargin; D000252:Calcium-Transporting ATPases; D011188:Potassium; D001920:Bradykinin