Calcium influx factor, further evidence it is 5,6-epoxyeicosatrienoic acid

Beverly A. Rzigalinski, Karen A. Willoughby, Stuart W. Hoffman, J R Falck, Earl F. Ellis

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Abstract

We present evidence in astrocytes that 5,6-epoxyeicosatrienoic acid, a cytochrome P450 epoxygenase metabolite of arachidonic acid, may be a component of calcium influx factor, the elusive link between release of Ca2+ from intracellular stores and capacitative Ca2+ influx. Capacitative influx of extracellular Ca2+ was inhibited by blockade of the two critical steps in epoxyeicosatrienoic acid synthesis: release of arachidonic acid from phospholipid stores by cytosolic phospholipase A2 and cytochrome P450 metabolism of arachidonic acid. AAOCF3, which inhibits cytosolic phospholipase A2, blocked thapsigargin-stimulated release of arachidonic acid as well as thapsigargin-stimulated elevation of intracellular free calcium. Inhibition of P450 arachidonic acid metabolism with SKF525A, econazole, or N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide, a substrate inhibitor of P450 arachidonic acid metabolism, also blocked thapsigargin-stimulated Ca2+ influx. Nanoto picomolar 5,6- epoxyeicosatrienoic acid induced [Ca2+](i) elevation consistent with capacitative Ca2+ influx. We have previously shown that 5,6- epoxyeicosatrienoic acid is synthesized and released by astrocytes. When 5,6- epoxyeicosatrienoic acid was applied to the rat brain surface, it induced vasodilation, suggesting that calcium influx factor may also serve a paracrine function. In summary, our results suggest that 5,6- epoxyeicosatrienoic acid may be a component of calcium influx factor and may participate in regulation of cerebral vascular tone.

Original languageEnglish (US)
Pages (from-to)175-182
Number of pages8
JournalJournal of Biological Chemistry
Volume274
Issue number1
DOIs
StatePublished - Jan 1 1999

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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