Related Experiment Videos
Calcium antagonistic actions of tetrandrine depend on cell types
H Takemura1, C Y Kwan, H Ohshika
1Department of Pharmacology, School of Medicine, Sapporo Medical University, Japan.
Abstract:
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.
Insights
Tetrandrine (TET) affects calcium (Ca2+) entry differently across various cell types. This study shows TET
Area of Science:
- Cellular Biology
- Pharmacology
- Physiology
Background:
- Calcium (Ca2+) signaling is crucial for numerous cellular functions.
- Understanding how compounds modulate Ca2+ entry is vital for therapeutic development.
- Tetrandrine (TET) is a known compound with potential effects on ion channels.
Purpose of the Study:
- To investigate the impact of tetrandrine (TET) on Ca2+ mobilization and entry in diverse cell models.
- To compare TET's effects with thapsigargin (TG), a tool for studying capacitative Ca2+ entry.
- To determine if TET's action on Ca2+ entry is cell-type specific.
Main Methods:
- Utilized inositol trisphosphate-generating drugs and thapsigargin (TG) to stimulate Ca2+ release and entry.
- Administered 100 μM tetrandrine (TET) to various cell lines, including PC12, NIH/3T3, C6, rat parotid acinar cells, and Jurkat cells.
- Measured intracellular calcium ([Ca2+]i) changes in response to stimuli in the presence and absence of TET.
Main Results:
- TET abolished or partially inhibited Ca2+ entry induced by various agonists and TG in PC12, NIH/3T3, C6, and rat parotid acinar cells.
- In Jurkat T-cells, TET did not inhibit Ca2+ entry evoked by anti-CD3 antibody or TG.
- The inhibitory effects of TET on Ca2+ entry were found to be cell-type dependent.
Conclusions:
- Tetrandrine (TET) significantly impacts Ca2+ mobilization and entry pathways in a cell-specific manner.
- The compound's effectiveness in modulating Ca2+ entry varies depending on the cell type and the stimulus used.
- These findings highlight the complex pharmacology of TET and its potential for differential targeting in various tissues.