Suramin and disulfonated stilbene derivatives stimulate the Ca2+-induced Ca2+ -release mechanism in A7r5 cells.
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.
Nadif Kasri
Nael
N
Laboratorium voor Fysiologie, Katholieke Universiteit Leuven Campus Gasthuisberg Herestraat 49/802, B-3000 Leuven, Belgium.
Bultynck
Geert
G
Parys
Jan B
JB
Callewaert
Geert
G
Missiaen
Ludwig
L
De Smedt
Humbert
H
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013267:Stilbenes / Q000737:chemistry / Q000494:pharmacology*; D013498:Suramin / Q000737:chemistry / Q000494:pharmacology*
D013267:Stilbenes; D013498:Suramin; D002118:Calcium