Lithium, used to treat
bipolar disorder, has been reported to decrease rat brain
mRNA and
protein levels of cytosolic
phospholipase A(2) (cPLA(2)), an
enzyme that selectively hydrolyzes
arachidonic acid from the stereospecifically numbered (sn)-2 position of membrane
phospholipids, and to decrease PLA(2) activity. cPLA(2) can be activated by being phosphorylated at its Ser-228, Ser-505, and Ser-727 sites. In this study, we show that the percent phosphorylated cPLA(2)
protein in rat brain is unaffected by
lithium. Male Fischer-344 rats were fed
lithium chloride for 6 weeks, so as to produce a therapeutically equivalent brain
lithium concentration; control rats were fed
lithium-free chow under parallel conditions. cPLA(2) was immunoprecipitated from brain homogenate and phosphorylated cPLA(2)
protein was quantified using an anti-
phosphoserine antibody, and compared to net cPLA(2)
protein. The mean ratio of phosphorylated/total cPLA(2) was not changed significantly in the
lithium-treated compared to the control group. Thus, decreased brain PLA(2)
enzyme activity caused by chronic
lithium is likely a consequence only of
lithium's downregulation of cPLA(2) transcription.