Effect of NPC-14686 (Fmoc-L-homophenylalanine) on intracellular Ca2+ levels in human hepatoma cells.

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.

• 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)

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

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)