D609, an inhibitor of phosphatidylcholine-specific phospholipase C, inhibits group IV cytosolic phospholipase A2.
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 A2 (cPLA2), but neither secretory PLA2 nor a Ca2+ -dependent PLA2. Dixon plot analysis shows a mixed pattern of noncompetitive and uncompetitive inhibition with Ki = 86.25 microM for the cPLA2 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 approximately 375 microM, 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 cPLA2.
Kang
Mi Sun
MS
Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Jung
Sung Yun
SY
Jung
Kwang Mook
KM
Kim
Seok Kyun
SK
Ahn
Kyong Hoon
KH
Kim
Dae Kyong
DK
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D054513:Group IV Phospholipases A2 / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D001952:Bridged-Ring Compounds; D004791:Enzyme Inhibitors; D009636:Norbornanes; D013859:Thiocarbamates; D013871:Thiones; D016718:Arachidonic Acid; C046498:tricyclodecane-9-yl-xanthogenate; D054513:Group IV Phospholipases A2; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C