Description
U-
73122 is an inhibitor of PLC-
dependent processes, however, the mechanism of action remains unclear. The IC
50 values for inhibition of platelet aggregation induced by collagen or thrombin are 0.6 and 5 μM, respectively. It also exhibits inhibitory activity against HIV-
1 integrase with an IC
50 value of 7 μM.
Uses
It is used as a phospholipase C, phospholipase A2, and 5-LO inhibitor. It is also determined that in SK-N-SH neuroblastoma cells, U-73122 inhibits agonist-induced down-regulation of muscarinic receptors. In addition, it is a useful tool to investigate receptor-mediated PI turnover in signal transduction. U-73122 is a potent inhibitor of human neutrophil adhesion to biological surfaces (IC50 = 50 nM) as well as adhesion-dependent granule exocytosis and oxidative burst. U-73343 (sc-201422) is useful as a negative control for investigations of U-73122 phospholipase C antagonism and its cellular consequences.
Definition
ChEBI: An aza-steroid that is 3-O-methyl-17beta-estradiol in which the 17beta-hydroxy group is replaced by a 6-(maleimid-1-yl)hexylamino group. An inibitor of phospholipase C.
Biological Activity
Phospholipase C inhibitor. Inhibits agonist-induced platelet aggregation with IC 50 values of 1-5 μ M. Potently inhibits human polymorphonuclear neutrophil adhesion on biological surfaces (IC 50 < 50 nM) and exhibits antinociceptive activity in vivo .
Biochem/physiol Actions
Inhibits the hydrolysis of PPI to IP3, which leads to a decrease in cytosolic free calcium. Inhibits the coupling of G protein-phospholipase C activation, while remaining unaffected by production of cAMP.
References
1) Bleasdale?et al. (1990),?Selective inhibition of receptor-coupled phospholipase C-dependent processes in human platelets and polymorphonuclear neutrophils; J. Pharmacol. Exp. Ther.,?255?756
2) Zholos?et al.?(2004),?Phospholipase C, but not InsP3 or DAG,-dependent activation of the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle cells; Br. J. Pharmacol.,?141?23
3) Jun?et al. (2004),?Diacylglycerol and its formation by phospholipase C regulate Rab- and SNARE dependent yeast vacuole fusion; J. Biol. Chem. ,279?53186
4) Fernandez-Ulibarri?et al.?(2007),?Diacylglycerol is required for the formation of COPI vesicles in the Golgi-to-ER transport pathway; Mol. Biol. Cell,?18?3250
