Phosphatidic acid induces calcium influx in neutrophils via verapamil-sensitive calcium channels
✍ Scribed by Rafat A. Siddiqui; Daniel J. Burtschi; Richard Kovacs
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 147 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Phosphatidic acid (PA) induces a biphasic Ca 2ϩ mobilization response in human neutrophils. The initial increase is due to the mobilization of Ca 2ϩ from intracellular stores, whereas the secondary increase is due to the influx of Ca 2ϩ from extracellular sources. The present investigation characterizes PA-induced Ca 2ϩ influx in neutrophils. Depolarization of neutrophils by 50 mM KCl enhanced PA-induced Ca 2ϩ influx, whereas verapamil, a Ca 2ϩ channel blocker, attenuated this response in a dose-dependent manner. These observations suggest that PA-induced Ca 2ϩ influx is mediated via verapamil-sensitive Ca 2ϩ channels. Stimulation of neutrophils with exogenous PA results in accumulation of endogenously generated PA with a time course similar to the effects of exogenous PA on Ca 2ϩ influx. Ethanol inhibited the accumulation of endogenous PA and calcium mobilization, indicating that activation of membrane phospholipase D plays a role in PA-mediated Ca 2ϩ influx. The results of this study suggest that exogenously added PA stimulates the generation of intracellular PA, which then mediates Ca 2ϩ influx through verapamil-sensitive Ca 2ϩ channels.