The effects of the phospholipase A2 inhibitors aristolochic acid and PGBx on A23187-stimulated mobilization of arachidonate in human neutrophils are overcome by diacylglycerol or phorbol ester
| Autor: | Richard C. Franson, Miriam D. Rosenthal, Kim S. Lattanzio |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Neutrophils
Polymers Phosphatidate Phosphatase Biophysics Aristolochic acid Phospholipase Biochemistry Phospholipases A Diglycerides chemistry.chemical_compound Endocrinology Phospholipase A2 Sphingosine Superoxides Phospholipase D Humans Diglyceride Calcimycin Protein kinase C Phospholipase A Arachidonic Acid Prostaglandins B biology Chemistry Phenanthrenes N-Formylmethionine Leucyl-Phenylalanine Phospholipases A2 biology.protein Aristolochic Acids Tetradecanoylphorbol Acetate Arachidonic acid |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism. 1126:319-326 |
| ISSN: | 0005-2760 |
| Popis: | Aristolochic acid and PGBx, two structurally unrelated, protein-targeted inhibitors of isolated phospholipases A2, are effective antagonists of calcium ionophore A23187-stimulated mobilization of [3H]arachidonate from human neutrophils. We now report that preincubation of neutrophils with oleoylacetylglycerol (OAG, 15 microM) substantially reverses the inhibitory effect of 200 microM aristolochic acid (from 70 to 24% inhibition). Similarly, OAG increases the IC50 for PGBx from 2.5 to greater than 20 microM. The effects of OAG on inhibition by either aristolochic acid or PGBx are dose-dependent, with an ED50 of 2.5 microM. Protection against inhibition by either aristolochic acid or PGBx is also observed with phorbol myristate acetate (PMA, ED50 3 nM), but not 4-alpha-phorbol didecanoate. Aristolochic acid and PGBx do not inhibit PMA-stimulated superoxide generation, and are thus not protein kinase C inhibitors. Furthermore, neither aristolochic acid nor PGBx inhibit diglyceride generation through the phospholipase D/phosphatidate phosphohydrolase pathway. A23187-stimulated [3H]arachidonate mobilization is increased by 20-50% when neutrophils are preincubated with OAG or PMA. The present results indicate that OAG and PMA also modulate the A23187-stimulated [3H]arachidonate mobilization so as to render it less sensitive to inhibitors of phospholipase A2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|