Platelet activating factor induces dopamine release in PC-12 cell line.
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.
Bussolino
F
F
Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.
Tessari
F
F
Turrini
F
F
Braquet
P
P
Camussi
G
G
Prosdocimi
M
M
Bosia
A
A
D000310:Adrenal Gland Neoplasms / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004224:Diterpenes; D004298:Dopamine / Q000378:metabolism*; D046934:Ginkgolides; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D010673:Pheochromocytoma / Q000378:metabolism; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D001285:Atropine; C037913:CV 3988; D002217:Carbachol; C045856:ginkgolide B; D002118:Calcium; D004298:Dopamine