Inhibition by abruquinone A of phosphoinositide-specific phospholipase C activation in rat neutrophils.
In rat neutrophils, formyl-Met-Leu-Phe (fMLP)-induced phosphate formation was inhibited by abruquinone A (IC50 value about 32.7 +/- 6.4 microM) as well as by a putative phospholipase C inhibitor, [6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole- 2,5-dione (U73122) (IC50 value about 11.3 +/- 1.2 microM). The reduction in inositol phosphate levels appeared to reflect inhibition of phospholipase C activity because the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) catalyzed by a soluble fraction from neutrophils was also inhibited by abruquinone A (IC50 value about 31.4 +/- 5.6 microM) over the same range of concentrations. Although abruquinone A alone induced Ca2+ and Mn2+ influx into neutrophils in Ca(2+)-containing medium, abruquinone A, like U73122, inhibited Ca2+ release (IC50 value about 23.5 +/- 0.5 microM) from internal stores in Ca(2+)-free medium. These results indicate that abruquinone A inhibits the activity of phosphoinositide-specific phospholipase C in neutrophils.
Wang
J P
JP
Department of Medical Research, Taichung Veterans General Hospital, Taiwan, ROC.
Hsu
M F
MF
Kuo
S C
SC
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D016227:Benzoquinones / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004789:Enzyme Activation; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D016227:Benzoquinones; D010716:Phosphatidylinositols; D009240:N-Formylmethionine Leucyl-Phenylalanine; C093391:abruquinone A; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium