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AJP - Cell Physiology, Vol 255, Issue 4 C559-C565, Copyright © 1988 by American Physiological Society
ARTICLES |
F. Bussolino, F. Tessari, F. Turrini, P. Braquet, G. Camussi, M. Prosdocimi and A. Bosia
Dipartimento di Genetica, Biologia e Chimica Medica, Universita di Torino, Italy.
The ability of platelet activating factor (PAF) to stimulate dopamine release and modify calcium homeostasis in PC-12 cell line was studied. PAF-induced dopamine release is related to its molecular form, with only the R-form steric configuration [(R)PAF], but not its S-form or its 2-lyso derivative, effective at being active. In addition, PAF acts at very low concentrations in a dose-dependent manner (0.1-30 nM). Preincubation with PAF receptor antagonists (CV-3988 and BN52021) as well as the specific desensitization of PC-12 cells to (R)PAF abolish the (R)PAF-induced dopamine release. Several lines of evidence suggest that dopamine release is dependent on a (R)PAF-induced calcium influx and efflux modulation. Dopamine release by PC-12 cells challenged with (R)PAF is associated with a rapid 45Ca influx and efflux and a rise in cytoplasmic calcium concentrations ([Ca2+]i) evaluated by using the calcium indicators fura-2 and quin2. At 30 nM (R)PAF, the absence of extracellular calcium inhibits the dopamine release but not the rise of [Ca2+]i from the internal stores, suggesting the importance of calcium influx in (R)PAF-induced dopamine release. PAF, which has been reported to be synthesized by stimulated neuronal cells (J. Biol. Chem. 261: 16502-16508, 1986) may thus have a physiological modulatory role on cells with neurosecretory properties.
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