Abstract |
The effect of NPC-14686, a potential anti-inflammatory drug, on cytosolic free Ca(2+) levels ([Ca(2+)](i)) in HA22/VGH human hepatoma cells was explored by using fura-2 as a fluorescent Ca(2+) indicator. NPC-14686 at concentrations above 10 microM increased [Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 100 microM. The Ca(2+) signal was reduced by removing extracellular Ca(2+) or by 10 microM nifedipine and was not changed by verapamil or diltiazem. Pretreatment with 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) abolished 200 microM NPC-14686-induced Ca(2+) release; and conversely pretreatment with NPC-14686 abolished thapsigargin-induced Ca(2+) release. The Ca(2+) release induced by 200 microM NPC-14686 was not changed by inhibiting phospholipase C with 2 microM U73122. Together, the results suggest that in human hepatoma cells, NPC-14686 induced a [Ca(2+)](i) increase by causing store Ca(2+) release from the endoplasmic reticulum in an phospholipase C-independent manner, and by inducing nifedipine-sensitive Ca(2+) influx.
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Authors | Chung-Ren Jan, Soong-Yu Kuo, Jin-Shiung Cheng, Yuk-Keung Lo, Chun-Peng Liu, Wei-Chung Chen |
Journal | Life sciences
(Life Sci)
Vol. 72
Issue 23
Pg. 2571-80
(Apr 25 2003)
ISSN: 0024-3205 [Print] Netherlands |
PMID | 12672503
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aminobutyrates
- Calcium Channel Blockers
- Drug Combinations
- Estrenes
- Fluorescent Dyes
- NPC 14686
- Pyrrolidinones
- 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
- Thapsigargin
- Type C Phospholipases
- Calcium
- Fura-2
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Topics |
- Aminobutyrates
(pharmacology)
- Calcium
(metabolism)
- Calcium Channel Blockers
(pharmacology)
- Calcium Signaling
(drug effects)
- Carcinoma, Hepatocellular
(metabolism)
- Dose-Response Relationship, Drug
- Drug Combinations
- Estrenes
(pharmacology)
- Fluorescent Dyes
- Fura-2
(metabolism)
- Hepatocytes
(drug effects, metabolism)
- Humans
- Pyrrolidinones
(pharmacology)
- Thapsigargin
(pharmacology)
- Tumor Cells, Cultured
- Type C Phospholipases
(antagonists & inhibitors)
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