D609, an Inhibitor of Phosphatidylcholine-specific Phospholipase C, Inhibits Group IV Cytosolic Phospholipase A(2)

Abstract

As an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), D609 has been widely used to explain the role of PC-PLC in various signal transduction pathways. This study shows that D609 inhibits group IV cytosolic phospholipase A(2) (cPLA(2)), but neither secretory PLA(2) nor a Ca2+-dependent PLA(2). Dixon plot analysis shows a mixed pattern of noncompetitive and uncompetitive inhibition with K-i = 86.25 mu M for the cPLA(2) purified from bovine spleen. D609 also time- and dose-dependently reduces the release of arachidonic acid from a Ca2+- ionophore A23187-stimulated MDCK cells. In the AA release experiment, IC50 of D609 was similar to 375 mu M, suggesting that this reagent may not enter the cells easily. The present study indicates that the inhibitory effects of D609 on various cellular responses may be partially attributable to the inhibition of cPLA(2).