Stimulation of platelet-activating factor (PAF) receptors increases inositol phosphate production and cytosolic free Ca2+ concentrations in N1E-115 neuroblastoma cells

Autor: M. Ziade, Jean Verdetti, M. Diserbo, F. Cand
Rok vydání: 1995
Předmět:
Zdroj: Cell calcium. 17(6)
ISSN: 0143-4160
Popis: Platelet-activating factor (1-O-alkyl-2-acetyl- sn -glycero-3-phosphorylcholine, PAF) has recently been recognized as an important mediator in the pathophysiology of brain injury. This study demonstrates that, in suspended populations of N1E-115 cells loaded with Indo-1, biologically relevant concentrations of PAF produce a rapid and transient elevation in cytosolic free calcium concentration ([Ca 2+ ] i ). Moreover, nanomolar concentrations of PAF increase [ 3 H]-inositol phosphate production. Using lyso-PAF and the specific PAF-receptor antagonists BN52021 and BN50739, we show that these effects were mediated by stimulation of PAF receptors. Experiments performed in Ca 2+ free medium show that PAF-induced [Ca 2+ ] i increase is the result of an influx of Ca 2+ and of the release of intracellular Ca 2+ stores. Studies of Mn 2+ influx argue in favour of additional pathways for the PAF-induced Ca 2+ influx other than the pathway for the thapsigargin-induced Ca 2+ influx. Using the whole-cell voltage-clamp technique, we observe that PAF induces an increase of Ltype Ca 2+ current. However, the effects of La 3+ , nifedipine and KCI-induced depolarization on the PAF-induced [Ca 2+ ] i increase suggest a minor participation of these voltage-gated Ca 2+ channels in the response to PAR Altogether the results point to the existence of a PAF-induced Ca 2+ influx through receptor-operated Ca 2+ permeant channels.
Databáze: OpenAIRE