Extracellular-derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid

Journal of Lipid Research

Angelo O. Rosa¹  Mireille Basselin²  Lisa Chang²  Stanley I. Rapoport²  Mei Chen²  Epolia Ramadan³ 

[1] Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD;Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD;To whom correspondence should be addressed;

关键词: arachidonic;    calcium;    cPLA2;    iPLA2;    NMDA;    MK-801;   

DOI  :  

来源: DOAJ

【 摘 要 】

In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca2+-independent phospholipase A2 (iPLA2), Ca2+-independent plasmalogen PLA2 or secretory PLA2 (sPLA2), but not by Ca2+-dependent cytosolic PLA2 (cPLA2), 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 cPLA2. DHA signaling may be mediated by iPLA2, plasmalogen PLA2, or other enzymes insensitive to low concentrations of Ca2+. Greater AA than DHA release during glutamate-induced excitotoxicity could cause brain cell damage.

【 授权许可】

Unknown