RRC ID 10926
Author Broad LM, Braun FJ, Lievremont JP, Bird GS, Kurosaki T, Putney JW Jr.
Title Role of the phospholipase C-inositol 1,4,5-trisphosphate pathway in calcium release-activated calcium current and capacitative calcium entry.
Journal J Biol Chem
Abstract We investigated the putative roles of phospholipase C, polyphosphoinositides, and inositol 1,4,5-trisphosphate (IP(3)) in capacitative calcium entry and calcium release-activated calcium current (I(crac)) in lacrimal acinar cells, rat basophilic leukemia cells, and DT40 B-lymphocytes. Inhibition of phospholipase C with blocked calcium entry and I(crac) activation whether in response to a phospholipase C-coupled agonist or to calcium store depletion with thapsigargin. Run-down of cellular polyphosphoinositides by concentrations of wortmannin that block phosphatidylinositol 4-kinase completely blocked calcium entry and I(crac). The membrane-permeant IP(3) receptor inhibitor, 2-aminoethoxydiphenyl borane, blocked both capacitative calcium entry and I(crac). However, it is likely that 2-aminoethoxydiphenyl borane does not inhibit through an action on the IP(3) receptor because the drug was equally effective in wild-type DT40 B-cells and in DT40 B-cells whose genes for all three IP(3) receptors had been disrupted. Intracellular application of another potent IP(3) receptor antagonist, heparin, failed to inhibit activation of I(crac). Finally, the inhibition of I(crac) activation by or wortmannin was not reversed or prevented by direct intracellular application of IP(3). These findings indicate a requirement for phospholipase C and for polyphosphoinositides for activation of capacitative calcium entry. However, the results call into question the previously suggested roles of IP(3) and IP(3) receptor in this mechanism, at least in these particular cell types.
Volume 276(19)
Pages 15945-52
Published 2001-5-11
DOI 10.1074/jbc.M011571200
PII S0021-9258(19)32011-3
PMID 11278938
MeSH Androstadienes / pharmacology Animals B-Lymphocytes Boron Compounds / pharmacology Calcium / metabolism Calcium / physiology* Calcium Channels / drug effects Calcium Channels / genetics Calcium Channels / physiology Cell Line, Transformed Cells, Cultured Chickens Enzyme Inhibitors / pharmacology Estrenes / pharmacology Heparin / pharmacology Inositol 1,4,5-Trisphosphate / metabolism* Inositol 1,4,5-Trisphosphate Receptors Kinetics Lacrimal Apparatus / cytology Lacrimal Apparatus / drug effects Lacrimal Apparatus / metabolism* Leukemia, Basophilic, Acute Mice Phosphatidylinositol Phosphates / metabolism* Pyrrolidinones / pharmacology Rats Receptors, Cytoplasmic and Nuclear / drug effects Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / physiology Thapsigargin / pharmacology Tumor Cells, Cultured Type C Phospholipases / metabolism* Wortmannin
IF 4.238
Times Cited 175
Human and Animal Cells DT40(RCB1464) IP3R^(-) DT40(RCB1467)