Journal
JOURNAL OF LIPID RESEARCH
Volume 51, Issue 8, Pages 2334-2340Publisher
ELSEVIER
DOI: 10.1194/jlr.M006262
Keywords
arachidonic; calcium; cPLA(2); iPLA(2); NMDA; MK-801; imaging
Categories
Funding
- National Institutes of Health
- National Institute on Aging
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In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca2+-independent phospholipase A(2) (iPLA(2)), Ca2+-independent plasmalogen PLA(2) or secretory PLA(2) (sPLA(2)), but not by Ca2+-dependent cytosolic PLA(2) (cPLA(2)), which selectively releases arachidonic acid (AA). Since glutamatergic NMDA (N-methyl-D-aspartate) receptor activation allows extracellular Ca2+ into cells, we hypothesized that brain DHA signaling would not be altered in rats given NMDA, to the extent that in vivo signaling was mediated by Ca2+-independent mechanisms. Isotonic saline, a subconvulsive dose of NMDA (25 mg/kg), MK-801, or MK-801 followed by NMDA was administered i.p. to unanesthetized rats. Radiolabeled DHA or AA was infused intravenously and their brain incorporation coefficients k*, measures of signaling, were imaged with quantitative autoradiography. NMDA or MK-801 compared with saline did not alter k* for DHA in any of 81 brain regions examined, whereas NMDA produced widespread and significant increments in k* for AA. In conclusion, in vivo brain DHA but not AA signaling via NMDA receptors is independent of extracellular Ca2+ and of cPLA(2). DHA signaling may be mediated by iPLA 2, plasmalogen PLA(2), or other enzymes insensitive to low concentrations of Ca2+. Greater AA than DHA release during glutamate-induced excitotoxicity could cause brain cell damage.-Ramadan, E., A. O. Rosa, L. Chang, M. Chen, S. I. Rapoport, and M. Basselin. Extracellular- derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid. J. Lipid Res. 2010. 51: 2334-2340.
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