STIMULATION OF PLATELET-ACTIVATING-FACTOR (PAF) RECEPTORS INCREASES INOSITOL PHOSPHATE PRODUCTION AND CYTOSOLIC-FREE CA2+ CONCENTRATIONS IN N1E-115 NEUROBLASTOMA-CELLS

被引:17
作者
DISERBO, M [1 ]
CAND, F [1 ]
ZIADE, M [1 ]
VERDETTI, J [1 ]
机构
[1] UNIV GRENOBLE 1, ELECTROPHYSIOL MOLEC GRP, GRENOBLE, FRANCE
关键词
D O I
10.1016/0143-4160(95)90090-X
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 ([Ca2+](i)). Moreover, nanomolar concentrations of PAF increase [H-3]-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 [Ca2+](i) increase is the result of an influx of Ca2+ and of the release of intracellular Ca2+ stores. Studies of Mn2+ influx argue in favour of additional pathways for PAF-induced Ca2+ influx other than the pathway for the thapsigargin-induced Ca2+ influx. Using the whole-cell voltage-clamp technique, we observe that PAF induces an increase of Ltype Ca2+ current. However, the effects of La3+, nifedipine and KCI-induced depolarization on the PAF-induced [Ca2+](i) increase suggest a minor participation of these voltage-gated Ca2+ channels in the response to PAF, Altogether the results point to the existence of a PAF-induced Ca2+ influx through receptor-operated Ca2+ permeant channels.
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页码:442 / 452
页数:11
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