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Dopamine D 2 Receptors Potentiate Arachidonate Release via Activation of Cytosolic, Arachidonate‐Specific Phospholipase A 2
Author(s) -
Vial Daniel,
Piomelli Daniele
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.64062765.x
Subject(s) - chinese hamster ovary cell , receptor , biology , dopamine receptor d2 , phospholipase c , second messenger system , phospholipase a2 , arachidonic acid , biochemistry , phospholipase , microbiology and biotechnology , enzyme
Several G i ‐linked neurotransmitter receptors, including dopamine D 2 receptors, act synergistically with Ca 2+ ‐mobilizing stimuli to potentiate release of arachidonic acid (AA) from membrane phospholipids. In brain, AA and its metabolites are thought to act as intracellular second messengers, suggesting that receptor‐dependent potentiation of AA release may participate in neuronal transmembrane signaling. To study the molecular mechanisms underlying this modulatory response, we have now used Chinese hamster ovary cells transfected with rat D 2 ‐receptor cDNA, CHO(D 2 ). Two antisense oligodeoxynucleotides corresponding to distinct cDNA sequences of cytosolic, AA‐specific phospholipase A 2 (cPLA 2 ) were synthesized and added to cultures of CHO(D 2 ) cells. Incubation with antisense oligodeoxynucleotides inhibited D 2 receptor‐dependent release of AA but had no effect on D 2 ‐receptor binding or D 2 inhibition of cyclic AMP accumulation. In addition, pharmacological experiments showed that D 2 receptor‐dependent AA release was prevented by nonselective phospholipase inhibitors (such as mepacrine) but not by inhibitors of membrane‐bound, non‐AA‐specific PLA 2 (such as p ‐bromophenacyl 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 serve a similar signaling function in brain.