Extracellular-derived calcium does not initiate in vivo neurotransmission involving docosahexaenoic acid.
In vitro studies show that docosahexaenoic acid (DHA) can be released from membrane phospholipid by Ca(2+)-independent phospholipase A(2) (iPLA(2)), Ca(2+)-independent plasmalogen PLA(2) or secretory PLA(2 (sPLA2)), but not by Ca(2+)-dependent cytosolic PLA(2) (cPLA2), which selectively releases arachidonic acid (AA). Since glutamatergic NMDA (N-methyl-D-aspartate) receptor activation allows extracellular Ca(2+) 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 Ca(2+)-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 Ca(2+) and of cPLA(2). DHA signaling may be mediated by iPLA(2), plasmalogen PLA(2), or other enzymes insensitive to low concentrations of Ca(2+). Greater AA than DHA release during glutamate-induced excitotoxicity could cause brain cell damage.
Ramadan
Epolia
E
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. ramadanir@mail.nih.gov
Rosa
Angelo O
AO
Chang
Lisa
L
Chen
Mei
M
Rapoport
Stanley I
SI
Basselin
Mireille
M
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001345:Autoradiography; D001921:Brain / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D057054:Molecular Imaging; D016202:N-Methylaspartate / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D009435:Synaptic Transmission
D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002118:Calcium
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