Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation.

Abstract

In this study, we have investigated responses to the phospholipase C (PLC) activator m-3M3FBS in SH-SY5Y human neuroblastoma cells. As measured using fura-2, m-3M3FBS caused a slowly developing - full response was obtained within 4-6 min - Ca(2+) elevation both in the presence and absence of extracellular Ca(2+), indicating Ca(2+) release from intracellular stores, putatively from endoplasmic reticulum and mitochondria. PLC activity was also measured using two methods, the classical ion-exchange separation and the more novel fluorescent real-time method. In the time frame in which m-3M3FBS caused Ca(2+) elevation (up to 7 min), no PLC activation was detected. Instead, more than 20 min were required to see any inositol phosphate generation in response to m-3M3FBS. m-3M3FBS also interfered with store-operated Ca(2+) influx and Ca(2+) extrusion. In conclusion, m-3M3FBS cannot be considered either potent or specific PLC activator.

• Authors: Jelena Krjukova, Tomas Holmqvist, Alexander S Danis, Karl E O Akerman, Jyrki P Kukkonen
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 143 Issue 1 Pg. 3-7 (Sep 2004) ISSN: 0007-1188 [Print] England
• PMID: 15302681 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2,4,6-trimethyl-N-(meta-3-trifluoromethylphenyl)benzenesulfonamide
• Enzyme Activators
• Estrenes
• Fluorescent Dyes
• Muscarinic Agonists
• Phosphatidylinositol 4,5-Diphosphate
• Pyrrolidinones
• Receptors, Muscarinic
• Sulfonamides
• 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
• Type C Phospholipases
• Calcium
• Fura-2

Topics

• Animals
• CHO Cells
• Calcium (metabolism)
• Cell Line, Tumor
• Cricetinae
• Cytophotometry
• Enzyme Activation (drug effects)
• Enzyme Activators (pharmacology)
• Estrenes (pharmacology)
• Female
• Fluorescent Dyes
• Fura-2
• Homeostasis (drug effects)
• Humans
• Muscarinic Agonists (pharmacology)
• Phosphatidylinositol 4,5-Diphosphate (metabolism)
• Pyrrolidinones (pharmacology)
• Receptors, Muscarinic (drug effects)
• Signal Transduction (drug effects)
• Sulfonamides (pharmacology)
• Type C Phospholipases (antagonists & inhibitors, metabolism)