D609, an Inhibitor of Phosphatidylcholine-specific Phospholipase C, Inhibits Group IV Cytosolic Phospholipase A2

  • Kang, Mi Sun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Jung, Sung Yun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Jung, Kwang Mook (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Kim, Seok Kyun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Ahn, Kyong Hoon (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University) ;
  • Kim, Dae Kyong (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
  • Received : 2008.06.03
  • Accepted : 2008.07.21
  • Published : 2008.11.30

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 $Ca^{2+}$-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 $Ca^{2+}$- ionophore A23187-stimulated MDCK cells. In the AA release experiment, $IC_{50}$ of D609 was ${\sim375}{\mu}M$, 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 $cPLA_2$.

Keywords

AA release;$cPLA_2$;D609;DAG;MDCK cells;PC-PLC

Acknowledgement

Supported by : Chung-Ang University

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