Subject(s)
Anti-Bacterial Agents/pharmacology , Brain/enzymology , Enzyme Inhibitors/pharmacology , Macrolides , Sphingomyelin Phosphodiesterase/antagonists & inhibitors , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bacillus cereus/drug effects , Bacillus cereus/enzymology , Brain/drug effects , Carrageenan , Dinoprostone/biosynthesis , Edema/chemically induced , Edema/drug therapy , Kinetics , Lipopolysaccharides/pharmacology , Micromonospora/metabolism , Monocytes/drug effects , Monocytes/metabolism , Rats , Staphylococcus aureus/drug effects , Staphylococcus aureus/enzymologyABSTRACT
Scyphostatin is a specific inhibitor for mammalian neutral magnesium-dependent sphingomyelinase with a fifty percent inhibition concentration (IC50) value of 1.0 microM. When used to inhibit lysosomal acid sphingomyelinase, an approximately 50-fold greater concentration is required. In human peripheral monocytes, the compound inhibits bacterial lipopolysaccharide (LPS)-induced prostaglandin E2 production and LPS-induced interleukin-1beta production with IC50 values of 0.8 microM and 0.1 microM, respectively. In rat, p.o. administration of the compound has also been shown to inhibit carrageenin-induced paw edema. Thus, it is hoped that utility of scyphostatin as a pharmacological tool will contribute to our understanding of the role of ceramide in the cellular inflammation process.
