Intracellular- and extracellular-derived Ca(2+) influence phospholipase A(2)-mediated fatty acid release from brain phospholipids.

Docosahexaenoic acid (DHA) and arachidonic acid (AA) are found in high concentrations in brain cell membranes and are important for brain function and structure. Studies suggest that AA and DHA are hydrolyzed selectively from the sn-2 position of synaptic membrane phospholipids by Ca(2+)-dependent cytosolic phospholipase A(2) (cPLA(2)) and Ca(2+)-independent phospholipase A(2) (iPLA(2)), respectively, resulting in increased levels of the unesterified fatty acids and lysophospholipids. Cell studies also suggest that AA and DHA release depend on increased concentrations of Ca(2+), even though iPLA(2) has been thought to be Ca(2+)-independent. The source of Ca(2+) for activation of cPLA(2) is largely extracellular, whereas Ca(2+) released from the endoplasmic reticulum can activate iPLA(2) by a number of mechanisms. This review focuses on the role of Ca(2+) in modulating cPLA(2) and iPLA(2) activities in different conditions. Furthermore, a model is suggested in which neurotransmitters regulate the activity of these enzymes and thus the balanced and localized release of AA and DHA from phospholipid in the brain, depending on the primary source of the Ca(2+) signal.