DOPAMINE D-2 RECEPTORS POTENTIATE ARACHIDONATE RELEASE VIA ACTIVATIONOF CYTOSOLIC, ARACHIDONATE-SPECIFIC PHOSPHOLIPASE A(2)

Several G(i)-linked neurotransmitter receptors, including dopamine D-2 receptors, act synergistically with Ca2+-mobilizing stimuli to potent iate release of arachidonic acid (AA) from membrane phospholipids. In brain, AA and its metabolites are thought to act as intracellular seco nd messengers, suggesting that receptor-dependent potentiation of AA r elease may participate in neuronal transmembrane signaling, To study t he molecular mechanisms underlying this modulatory response, we have n ow used Chinese hamster ovary cells transfected with rat D-2-receptor cDNA, CHO(D-2). Two antisense oligodeoxynucleotides corresponding to d istinct cDNA sequences of cytosolic, AA-specific phospholipase A(2) (c PLA(2)) were synthesized and added to cultures of CHO(D-2) cells. Incu bation with antisense oligodeoxynucleotides inhibited D-2 receptor-dep endent release of AA but had no effect on D-2-receptor binding or D-2 inhibition of cyclic AMP accumulation. In addition, pharmacological ex periments showed that D-2 receptor-dependent AA release was prevented by nonselective phospholipase inhibitors (such as mepacrine) but not b y inhibitors of membrane-bound, non-AA-specific PLA(2) (such as p-brom ophenacyl bromide). cPLA(2) is expressed in brain tissue, The results, showing that cPLA(2) participates in receptor-dependent potentiation of AA release in CHO(D-2) cells, suggest that this phospholipase may s erve a similar signaling function in brain.