RT Journal Article
SR Electronic
T1 Suramin and Disulfonated Stilbene Derivatives Stimulate the Ca<sup>2+</sup>-Induced Ca<sup>2+</sup>-Release Mechanism in A7r5 Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 241
OP 250
DO 10.1124/mol.105.013045
VO 68
IS 1
A1 Nael Nadif Kasri
A1 Geert Bultynck
A1 Jan B. Parys
A1 Geert Callewaert
A1 Ludwig Missiaen
A1 Humbert De Smedt
YR 2005
UL http://molpharm.aspetjournals.org/content/68/1/241.abstract
AB We have described previously a novel Ca2+-induced Ca2+-release (CICR) mechanism in permeabilized A7r5 cells (embryonic rat aorta) and 16HBE14o-cells (human bronchial mucosa) cells (J Biol Chem 278:27548–27555, 2003). This CICR mechanism was activated upon the elevation of the free cytosolic calcium concentration [Ca2+]c and was not inhibited by pharmacological inhibitors of the inositol-1,4,5-trisphosphate (IP3) receptor nor of the ryanodine receptor. This CICR mechanism was inhibited by calmodulin (CaM)1234, a Ca2+-insensitive CaM mutant, and by different members of the superfamily of CaM-like Ca2+-binding proteins. Here, we present evidence that the CICR mechanism that is expressed in A7r5 and 16HBE14o-cells is strongly activated by suramin and 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS). We found several indications that both activation mechanisms are indeed two different modes of the same release system. Suramin/DIDS-induced Ca2+ release was only detected in cells that displayed the CICR mechanism, and cell types that do not express this type of CICR mechanism did not exhibit suramin/DIDS-induced Ca2+ release. Furthermore, we show that the suramin-stimulated Ca2+ release is regulated by Ca2+ and CaM in a similar way as the previously described CICR mechanism. The pharmacological characterization of the suramin/DIDS-induced Ca2+ release further confirms its properties as a novel CaM-regulated Ca2+-release mechanism. We also investigated the effects of disulfonated stilbene derivatives on IP3-induced Ca2+ release and found, in contrast to the effect on CICR, a strong inhibition by DIDS and 4′-acetoamido-4′-isothiocyanostilbene-2′,2′-disulfonic acid.