Add time:07/24/2019         Source:sciencedirect.com

1-[6-[[17β-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]-hexyl]1H-pyrrole-2,5-dione (U-73122 (cas 112648-68-7)) is an aminosteroid that was identified initially as a potent inhibitor of platelet activation by receptor-specific agonists. U-73122 inhibits receptor-coupled generation of inositol 1,4,5-trisphosphate (but not cyclic AMP) and intracellular mobilization of Ca 2+ in a variety of cell types. U-73122 inhibits phosphoinositide-specific phospholipase C (PI-PLC) activity in cell-free systems, but exhibits little or no direct inhibition of phospholipases A2 and D. Structure-activity analysis revealed that the maleimide group of U-73122 is essential, but not sufficient, for inhibitory activity. The succinimide analog of U-73122 (U-73343) has negligible inhibitory activity and is a useful control compound. On the basis of information derived from the use of U-73122 in a variety of cell types, procedures for storing, dissolving, and presenting U-73122 to cells are recommended. While knowledge of the mechanism of action of U-73122 would extend the utility of this compound, U-73122 has already been employed successfully to examine PI-PLC involvement in a variety of cellular processes. The application of U-73122 in an investigation of muscarinic receptor sequestration in SK-N-SH neuroblastoma cells is illustrated.

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