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] J E BLEASDALE. Selective inhibition of receptor-coupled phospholipase C-dependent processes in human platelets and polymorphonuclear neutrophils.[J]. Journal of Pharmacology and Experimental Therapeutics, 1990, 255 2: 756-768.
[2] ALEXANDER V ZHOLOS. Phospholipase C, but not InsP3 or DAG, -dependent activation of the muscarinic receptor-operated cation current in guinea-pig ileal smooth muscle cells[J]. British Journal of Pharmacology, 2009, 141 1: 23-36. DOI:
10.1038/sj.bjp.0705584[3] YOUNGSOO JUN William W Rutilio A Fratti. Diacylglycerol and its formation by phospholipase C regulate Rab- and SNARE-dependent yeast vacuole fusion.[J]. The Journal of Biological Chemistry, 2004: 53186-53195. DOI:
10.1074/jbc.m411363200[4] INÉS FERNÁNDEZ-ULIBARRI. Diacylglycerol is required for the formation of COPI vesicles in the Golgi-to-ER transport pathway.[J]. Molecular Biology of the Cell, 2007, 18 9: 3250-3263. DOI:
10.1091/mbc.e07-04-0334
