D-myo-inositol 1,3,4,5-tetrakisphosphate releases Ca2+ from crude microsomes and enriched vesicular plasma membranes, but not from intracellular stores of permeabilized T-lymphocytes and monocytes.
In the human T-lymphocyte cell lines Jurkat and HPB.ALL and the human monocytoid cell line U937, Ins(1,3,4,5)P4 triggers a dose-dependent release of Ca2+ from crude microsomal preparations, with a half-maximal effective concentration (EC50) of 1.2-2.3 microM. Similar results were obtained with enriched vesicular plasma membranes from U937 cells. However, in permeabilized preparations of the same cell types only Ins(1,4,5)P3 was able to release Ca2+ from intracellular stores, with EC50 values in the range 0.11-0.84 microM. In crude microsomes the effects of Ins(1,3,4,5)P4 and Ins(2,4,5)P3, a non-metabolizable InsP3 isomer, occurred independently of each other, indicating subpopulations of Ins(1,3,4,5)P4- and Ins(1,4,5)P3-sensitive vesicles. The Ins(1,3,4,5)P4 preparation used for the Ca(2+)-release experiments contains neither Ca2+ nor contaminating Ins(1,4,5)P3 and was not metabolized to Ins(1,4,5)P3 during the Ca(2+)-release experiments. We conclude that Ins(1,3,4,5)P4 independently of Ins(1,4,5)P3 induces a Ca2+ flux via a membrane compartment, most likely the plasma membrane, that is functionally destroyed during the permeabilization of the cells.
Guse
A H
AH
Max-Planck-Society, Clinical Research Unit for Rheumatology/Immunology, Institute for Clinical Immunology of the University, Erlangen, Federal Republic of Germany.
Roth
E
E
Emmrich
F
F
D002118:Calcium / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology*; D008861:Microsomes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium