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

Br J Pharmacol. 2004 Sep;143(1):3-7. doi: 10.1038/sj.bjp.0705911. Epub 2004 Aug 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Type C Phospholipases / metabolism*

Substances

  • 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