Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor.
Platelet-activating factor (PAF) is a naturally occurring phospholipid that serves as a critical mediator in diverse biological and pathophysiological processes. In this study of the interactions of PAF with neuronal cells, it was found that PAF increased the intracellular levels of free calcium ions in cells of the clones NG108-15 and PC12. The increase was dependent on extracellular calcium and was inhibited by the antagonistic PAF analog CV-3988 and by the calcium-influx blockers prenylamine and diltiazem. A functional consequence of this interaction was revealed by measuring a PAF-elicited, Ca2+-dependent secretion of adenosine triphosphate from PC12 cells. Exposure of NG108-15 cells for 3 to 4 days to low concentrations of PAF induced neuronal differentiation; higher concentrations were neurotoxic. Thus, by influencing Ca2+ fluxes, PAF may play a physiological role in neuronal development and a pathophysiological role in the degeneration that occurs when neurons are exposed to circulatory factors as a result of trauma, stroke, or spinal cord injury.
Kornecki
E
E
Department of Psychiatry, University of Vermont College of Medicine, Burlington 05405.
Ehrlich
Y H
YH
D000320:Adrenergic Fibers / Q000166:cytology; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002799:Cholinergic Fibers / Q000166:cytology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins; D010742:Phospholipid Ethers / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D009498:Neurotoxins; D010742:Phospholipid Ethers; D010972:Platelet Activating Factor; D001569:Benzodiazepines; C037913:CV 3988; D002118:Calcium