Calcium homeostasis in mouse fibroblast cells

Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms

J. P. Grierson, J. Meldolesi

Research output: Contribution to journalArticle

32 Citations (Scopus)

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

Fingerprint

Type C Phospholipases
Homeostasis
Fibroblasts
Calcium
Thapsigargin
Lysophosphatidic Acid Receptors
Uridine Triphosphate
Calcium-Transporting ATPases
Adenosine Diphosphate
Adenosine Triphosphate
Cell Membrane
Ligands
Cell Line
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Calcium homeostasis in mouse fibroblast cells : Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms. / Grierson, J. P.; Meldolesi, J.

In: British Journal of Pharmacology, Vol. 115, No. 1, 1995, p. 11-14.

Research output: Contribution to journalArticle

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