Calcium homeostasis in mouse fibroblast cells: affected by U-73122, a putative phospholipase C beta blocker, via multiple mechanisms

Br J Pharmacol. 1995 May;115(1):11-4. doi: 10.1111/j.1476-5381.1995.tb16312.x.


1. The inhibitory effects of the putative phospholipase C beta inhibitor, U-73122, on ligand-induced and thapsigargin-induced [Ca2+]i transients were investigated in mouse fibroblast cells (the L line). 2. Ca2+ release from intracellular stores was stimulated either by ATP (and also by UTP or ADP) working through the activation of a P2U receptor, or by lysophosphatidic acid, which elicited a more pronounced response. 3. U-73122 inhibited the Ca2+ mobilization produced by all the agonists in a dose-dependent manner, consistent with a mode of action involving phospholipase C inhibition. 4. In addition, however, U-73122 slowed the kinetics of intracellular Ca2+ release induced by the Ca(2+)-ATPase inhibitor, thapsigargin, and reduced the influx of Ca2+ across the plasma membrane, following stimulation of store-dependent influx by the latter. 5. We conclude that U-73122 has multiple sites of action, all of which can lead to a change in Ca2+ homeostasis. Thus, particular caution is recommended when employing this agent and when interpreting the results obtained.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Estrenes / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism*
  • Homeostasis / drug effects
  • L Cells
  • Mice
  • Pyrrolidinones / pharmacology*
  • Type C Phospholipases / antagonists & inhibitors*


  • Estrenes
  • Pyrrolidinones
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • Type C Phospholipases
  • Calcium