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

J. P. Grierson; J. Meldolesi

Calcium homeostasis in mouse fibroblast cells

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

J. P. Grierson, J. Meldolesi

IRCCS Ospedale San Raffaele

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	11-14
Number of pages	4
Journal	British Journal of Pharmacology
Volume	115
Issue number	1
Publication status	Published - 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

Grierson, J. P., & Meldolesi, J. (1995). Calcium homeostasis in mouse fibroblast cells: Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms. British Journal of Pharmacology, 115(1), 11-14.

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 journal › Article

Grierson, JP & Meldolesi, J 1995, 'Calcium homeostasis in mouse fibroblast cells: Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms', British Journal of Pharmacology, vol. 115, no. 1, pp. 11-14.

Grierson JP, Meldolesi J. Calcium homeostasis in mouse fibroblast cells: Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms. British Journal of Pharmacology. 1995;115(1):11-14.

Grierson, J. P. ; Meldolesi, J. / Calcium homeostasis in mouse fibroblast cells : Affected by U-73122, a putative phospholipase C(β) blocker, via multiple mechanisms. In: British Journal of Pharmacology. 1995 ; Vol. 115, No. 1. pp. 11-14.

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