Arachidonic acid and its metabolites increase Cai in cultured rat oligodendrocytes.
Fluorescence measurements of intracellular calcium (Cai) were made on cultured rat spinal cord oligodendrocytes (OLGs) using the dye fura-2. Exposure of OLGs to arachidonic acid (AA) (5-50 microM) elicited a concentration-dependent increase in Cai that was derived mainly from extracellular Ca2+. AA at 50 microM also released Ca2+ from intracellular stores. The response to AA was not decreased by nifedipine or by inhibition of Na(+)-Ca2+ exchange. AA-induced Ca2+ influx pathway was permeable to Mn2+ and Co2+ but not to Ba2+ and was not markedly influenced by depolarization, suggesting that AA activates a voltage-independent, not strictly selective, Ca2+ channel. The Cai response to AA was partially attenuated in the presence of indomethacin, indicating that the Cai response was mediated in part by cyclooxygenase products of AA. However, the AA-induced Cai response far exceeded that induced by prostaglandins and was mimicked by linoleic acid. We conclude that AA modulates Cai of OLGs via two mechanisms: 1) indirectly via cyclooxygenase pathway and 2) directly via membrane lipid-protein interaction.
Department of Neurology, University of Chicago, Illinois 60637.
B
B
Soliven
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M
Takeda
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T
Shandy
D J
DJ
Nelson
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003035:Cobalt / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005453:Fluorescence; D016257:Fura-2; D007213:Indomethacin / Q000494:pharmacology; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000494:pharmacology; D008345:Manganese / Q000493:pharmacokinetics; D009543:Nifedipine / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism / Q000502:physiology; D011453:Prostaglandins / Q000494:pharmacology; D051381:Rats
D001095:Arachidonic Acids; D015220:Calcium Channels; D008041:Linoleic Acids; D011453:Prostaglandins; D003035:Cobalt; D008345:Manganese; D019787:Linoleic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2; D007213:Indomethacin