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Extracellular ATP activates polyphosphoinositide breakdown and Ca2+ mobilization in Ehrlich ascites tumor cells.

Abstract：

:The effects of extracellular ATP on phosphoinositide metabolism and intracellular Ca2+ homeostasis were studied in Ehrlich ascites tumor cells. Cytosolic [Ca2+] was measured using either quin 2 or the recently described indicator fura 2. Addition of 0.5-25 microM extracellular ATP to intact cells results in a rapid mobilization of Ca2+ from a nonmitochondrial, intracellular Ca2+ store. Likewise, direct addition of 0.2-2 microM myo-1,4,5-inositol trisphosphate (IP3) to digitonin-permeabilized Ehrlich cells induces a rapid and reversible release of Ca2+ from a nonmitochondrial pool. Under the same conditions which facilitate intracellular Ca2+ mobilization, extracellular ATP also triggers a rapid breakdown of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and accumulation of IP3. A maximal 18% decrease of the polyphosphoinositide is observed 40-60 s after the addition of 25 microM ATP; within 5 min PtdIns(4,5)P2 returns to or exceeds the original, prestimulus level. These conditions also trigger a rapid accumulation of phosphatidic acid (1.7-fold increase within 5 min). Paralleling these ATP-induced changes in phospholipid levels is a substantial accumulation of the mono-, bis-, and trisphosphate derivatives of inositol; most significantly, a 2-fold increase in the IP3 level is observed within 30 s after ATP addition. These results suggest that in these tumor cells, extracellular ATP elicits changes in phosphoinositide metabolism similar to those produced by a wide variety of Ca2+-mobilizing hormones and growth factors.

journal_name

Arch Biochem Biophys

journal_title

Archives of biochemistry and biophysics

authors

Dubyak GR

doi

10.1016/0003-9861(86)90192-x

subject

Has Abstract

pub_date

1986-02-15 00:00:00

pages

84-95

issue

1

eissn

0003-9861

issn

1096-0384

pii

0003-9861(86)90192-X

journal_volume

245

pub_type

杂志文章

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