Possible Interaction: Phosphatidic Acid and Quinacrine

“Such synthesis of lysophosphatidic acid can be inhibited by mepacrine , an inhibitor of the phospholipase A2 which attacks phosphatidic acid to give lysophosphatidic acid.”

“…,mepacrine … phosphatidic acid in response to thrombin, consistent with some simultaneous inhibition of phospholipase C. Lysophosphatidic acid (2.5-22 microM) overcame the mepacrine block in … without stimulating the release of arachidonic acid from platelet phospholipids or the formation of lysophosphatidic acid, and only slightly increasing phosphatidic acid formation.”

“ Quinacrine (1 mM) caused 41% reduction in the amount of [3H]phosphatidic acid accumulated by the stimulation in [2-3H]glycerol-prelabeled cells.”

“The SRE stimulation by PA was dramatically reduced by either pre-treatment with mepacrine , an inhibitor of phospholipase A2 (PLA2), or co-transfection with antisense cytosolic phospholipase A2 (cPLA2) oligonucleotide, whereas lysophosphatidic acid (LPA)-induced SRE activation was not affected.”

“Quantitative analysis of these mepacrine effects, together with the known inhibitory effects of this compound on phospholipase A2 and phosphatidylinositol-specific phospholipase C, suggests that mepacrine also inhibits phosphatidic acid phosphatase, thereby shunting the flux of phosphatidic acid away from diglyceride formation and into synthesis of phosphatidylinositol.”

“ Mepacrine stimulated the labelling of phosphatidic acid , phosphatidylinositol and diacylglycerol, and inhibited that of phosphatidylcholine, phosphatidylethanolamine and triacylglycerol.”