Phosphatidic acid induces calcium influx in neutrophils via verapamil-sensitive calcium channels.
Phosphatidic acid (PA) induces a biphasic Ca(2+) mobilization response in human neutrophils. The initial increase is due to the mobilization of Ca(2+) from intracellular stores, whereas the secondary increase is due to the influx of Ca(2+) from extracellular sources. The present investigation characterizes PA-induced Ca(2+) influx in neutrophils. Depolarization of neutrophils by 50 mM KCl enhanced PA-induced Ca(2+) influx, whereas verapamil, a Ca(2+) channel blocker, attenuated this response in a dose-dependent manner. These observations suggest that PA-induced Ca(2+) influx is mediated via verapamil-sensitive Ca(2+) 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(2+) 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(2+) influx. The results of this study suggest that exogenously added PA stimulates the generation of intracellular PA, which then mediates Ca(2+) influx through verapamil-sensitive Ca(2+) channels.
Siddiqui
R A
RA
Cellular Biochemistry Laboratory, Methodist Research Institute, Indianapolis, Indiana. rsiddiqu@clarian.com
Burtschi
D J
DJ
Kovacs
R
R
D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010739:Phospholipase D / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010712:Phosphatidic Acids; D000431:Ethanol; D014700:Verapamil; D010739:Phospholipase D