Chronic lithium administration decreases the turnover of arachidonic a
cid (AA) in several brain phospholipids. This suggests that lithium ma
y attenuate phospholipase A(2) (PLA(2)) activity in brain. We now repo
rt effects of chronic lithium treatment on PLA(2) activity in postnucl
ear supernatant from rat brain: Enzyme activity was determined by two
assay methods, radiometric and fluorometric, and measured the release
of the fatty acid on the second acyl position (sn2) from choline and e
thanolamine phospholipids. PLA(2) activity in brain postnuclear supern
atant from rats chronically treated with lithium in the diet was signi
ficantly decreased (20-50%) when compared with controls. In vehicle or
lithium-treated rats, PLA(2) activity was not significantly augmented
or attenuated by the addition of calcium chelators, divalent cations
or LiCl supplementation (1.0 mM) to postnuclear supernatant. These res
ults suggest that a major therapeutic effect of lithium is to attenuat
e brain PLA(2) activity involved in signal transduction.