Description
ONO-RS-082 (99754-06-0) is a reversible inhibitor of Ca2+-independent phospholipase A2(PLA2), IC50=7 μM for guinea pig lung PLA2.1Inhibits epinephrine-induced thromboxane production in platelets.1Inhibition of PLA2by ONO-RS-032 disrupts endosome tubule formation and maintenance of the Golgi complex.2-4Prevents Xenopus oocyte maturation at stage V.5
in vitro
previous study found that human platelets stimulated by epinephrine led to enhanced turnover of phosphatidylinositol 4,5-bisphosphate, accumulated inositol trisphosphate, diacylglycerol, and phosphatidic acid, indicating stimulation of phospholipase c. it was shown that these responses could be completely blocked by inhibitors of alpha 2-adrenergic receptors including ono-rs-082 or removal of fibrinogen. in addition, epinephrine could evoked an increased turnover of ester-linked arachidonic acid in aspirin treated platelets that was inhibited by ono-rs-082 or the absence of fibrinogen. moreover, it was found that ono-rs-082 at 3.5 μm was able to inhibit epinephrine-stimulated thromboxane production in human platelets. ono-rs-082 could also disrupt endosome tubule formation and maintenance of the golgi complex [1].
References
[1] H S BANGA. Activation of phospholipases A and C in human platelets exposed to epinephrine: role of glycoproteins IIb/IIIa and dual role of epinephrine.[J]. Proceedings of the National Academy of Sciences of the United States of America, 1986, 83 23: 9197-9201. DOI:
10.1073/pnas.83.23.9197[2] P. DE FIGUEIREDO. Inhibition of Transferrin Recycling and Endosome Tubulation by Phospholipase A2 Antagonists*[J]. The Journal of Biological Chemistry, 2001, 27 1: 47361-47370. DOI:
10.1074/jbc.m108508200[3] JOHN A SCHMIDT. A role for phospholipase A2 activity in membrane tubule formation and TGN trafficking.[J]. Traffic, 2010, 11 12: 1530-1536. DOI:
10.1111/j.1600-0854.2010.01115.x[4] MARIE E BECHLER William J B. Gβ1γ2 activates phospholipase A2-dependent Golgi membrane tubule formation.[J]. Frontiers in Cell and Developmental Biology, 2014, 2 4: 0004. DOI:
10.3389/fcell.2014.00004[5] AZHARUL ISLAM . The distinct stage-specific effects of 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid on the activation of MAP kinase and Cdc2 kinase in Xenopus oocyte maturation[J]. Cellular signalling, 2005, 17 4: Pages 507-523. DOI:
10.1016/j.cellsig.2004.09.011
