Calcium homeostasis in mouse fibroblast cells: Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms

J. P. Grierson, J. Meldolesi

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Abstract

1. The inhibitory effects of the putative phospholipase C(β) 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 P(2U) 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 Ca2+-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.

Original languageEnglish
Pages (from-to)11-14
Number of pages4
JournalBritish Journal of Pharmacology
Volume115
Issue number1
Publication statusPublished - 1995

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Keywords

  • Calcium homeostasis
  • Fibroblast
  • Phospholipase C
  • Store-dependent Ca influx
  • Thapsigargin-induced Ca release
  • U-73122

ASJC Scopus subject areas

  • Pharmacology

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