Elsevier

Biochemical Pharmacology

Volume 53, Issue 8, 25 April 1997, Pages 1173-1177
Biochemical Pharmacology

Research paper
Impairment of phosphatidylinositol signaling in acetylshikonin-treated neutrophils

https://doi.org/10.1016/S0006-2952(97)00098-1Get rights and content

Abstract

In rat neutrophils, formylmethionyl-leucyl-phenylalanine (fMLP)-induced inositol phosphate formation was concentration-dependently inhibited by acetylshikonin as well as by a putative phospholipase C (PLC) inhibitor [6-[[17β-3-methoxyestra-l,3,5(10)-trien-17-yl]amino]hexy1]-lH-pyrrole-2,5-dione (U73122). The IC50 value of acetylshikonin for the inhibition of inositol trisphosphate (IP3) formation was estimated to be 16.1 ±1.5μM. The reduction of inositol phosphate levels appeared to reflect inhibition of PLC activity because the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) catalyzed by a soluble fraction from neutrophils was also inhibited by acetylshikonin (IC50value 21.4 ± 6.1μM) over the same range of concentrations. Although acetylshikonin alone evoked Ca2+ and Mn2+ influx into neutrophils in Ca2+-containing medium, acetylshikonin, like U73122, inhibited Ca2+ release (IC50value ~5.3 ± 0.4 μM) from internal stores in Ca2+-free medium. These results indicate that acetylshikonin inhibits phosphatidylinositol signaling in neutrophils.

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    This work was supported by a grant from the National Science Council of the Republic of China (NSC83-0420-B-075A-021 M03).

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