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

Abstract

-independent PLA2; sPLA2, secretory PLA2; PUFA, polyunsaturated fatty acid.

Imaging decreased brain docosahexaenoic acid metabolism and signaling in iPLA2β (VIA)-deficient mice

“…Muscarinic agonists also can release Ca 2+ from intracellular stores through the inositol-1,4,5-phosphate receptor ( 53,54 ) to indirectly activate iPLA 2 ␤ ( 16, 55 ). On the other hand, activation of ionotropic glutamatergic N -methyl -D -aspartate receptors by N -methyl-D -aspartate, which allows extracellular Ca 2+ into the cell, did not produce a measurable brain DHA signal in unanesthetized rats while producing a robust AA signal ( 17,56 ). These data are consistent with iPLA 2 being DHA selective and independent of extracellular Ca 2+ , but with cPLA 2 -IVA being AA selective and Ca 2+ -dependent ( 4, 6, 47, 57, 58 ).…”

“…iPLA 2 ␤ is an 84 Ϫ 88 kDa enzyme localized in the cell cytosol and endoplasmic reticulum. It is not activated by extracellular-derived Ca 2+ but may be activated when Ca 2+ is released from intracellular stores to displace inhibitory calmodulin from it ( 6,(12)(13)(14)(15)(16)(17). Mutations in the PLA2G6 gene encoding iPLA 2 ␤ have been associated with infantile neuroaxonal dystrophy, idiopathic neurodegeneration with brain iron accumulation ( 18,19 ), and adult-onset dystonia-parkinsonism without brain iron accumulation (20)(21)(22).…”

Docosahexaenoic acid (DHA) incorporation into the brain from plasma, as an in vivo biomarker of brain DHA metabolism and neurotransmission

“…Several groups of PLA 2 enzymes have been identified in the mammalian brain, and their specificity has been characterized based in vitro studies [35]. These include (1) AA-selective calcium-dependent cytosolic cPLA 2 type IVA, which can be activated via multiple G-protein-coupled neuroreceptors, including serotonergic 5-HT 2A/2C receptors [36,37] and muscarinic M 1,3,5 receptors [38], and the ionotropic N-methyl-D-aspartate (NMDA) receptor that when activated allows extracellular calcium into the cell [39]; (2) secretory presynaptic sPLA 2 which requires a high calcium concentration (20 mM) for activation, and (3) calcium-independent iPLA 2 , which is considered DHA-selective, and can be activated through both muscarinic and serotonergic receptors but not NMDA receptors [20,40,41]. Both cPLA 2 and iPLA 2 have post-synaptic locations in the mammalian brain [42,43].…”

Lamotrigine blocks NMDA receptor-initiated arachidonic acid signalling in rat brain: implications for its efficacy in bipolar disorder

“…When glutamate or NMDA binds to an NMDAR, extracellular Ca 2+ enters the cell and activates, among other enzymes, Ca 2+ -dependent-cytosolic phospholipase A 2 type IV (cPLA 2 -IV), which selectively releases arachidonic acid (AA, 20:4n-6) from cell membrane phospholipids (Basselin et al , 2006a; Basselin et al , 2008; Basselin et al , 2007a; Clark et al , 1991; Dumuis et al , 1988; Ramadan et al , 2010). Consistent with a hyperglutamatergic state, the postmortem BD brain shows up-regulated markers of AA metabolism, including cPLA 2 , cyclooxygenase (COX)-2, and membrane prostaglandin E synthase, which converts AA to pro-inflammatory prostaglandin (PG)E 2 (Kim et al , 2011).…”