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 |
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Pages (from-to) | 11-14 |
Number of pages | 4 |
Journal | British Journal of Pharmacology |
Volume | 115 |
Issue number | 1 |
Publication status | Published - 1995 |
Keywords
- Calcium homeostasis
- Fibroblast
- Phospholipase C
- Store-dependent Ca influx
- Thapsigargin-induced Ca release
- U-73122
ASJC Scopus subject areas
- Pharmacology