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• W2084539802 abstract "Recently, we provided evidence for cyclic adenosine 5′-diphosphate-ribose, cADP-ribose, as a second messenger in Jurkat T-lymphocytes upon stimulation of the T-cell receptor/CD3- complex (Guse et al., 1999). cADP-ribose mobilizes Ca2+ from an intracellular Ca2+ store which is sensitive to caffeine and gated by the ryanodine receptor/Ca2+ release channel. In the present study we investigated the ability of the trypanocidal drug, suramin, to activate the ryanodine receptor of T-cells. Since suramin cannot permeate the plasma membrane, it was necessary to microinject the drug into Fura-2 loaded T-lymphocytes. In a dose dependent manner suramin increased the intracellular Ca2+ concentration. The dose-response curve is very steep and calculates for an EC50 of 7.6±2.9 mM suramin in the injection pipette. Co-injection of the selective ryanodine receptor inhibitor ruthenium red completely abolished the suramin induced Ca2+ transient. This finding allows for the conclusion that the IP3-receptor sensitive Ca2+ pool is not the primary target of the suramin induced Ca2+ transient. Furthermore, Ins(1,4,6)PS3, an antagonist of the InsP3-receptor could not suppress the suramin-induced Ca2+ signal. The suramin induced Ca2+ transients declined very slowly; however, in the presence of Ins(1,4,6)PS3 this decay was accelerated. In addition, suramin did not interact with the cADP-ribose binding site of the ryanodine receptor of T-cells. In conclusion, suramin is found to be an agonist for the T-cell ryanodine receptor as previously found for the cardiac and skeletal muscle isoform. Therefore, suramin can be designated a universal ryanodine receptor agonist. British Journal of Pharmacology (1999) 128, 1235–1240; doi:10.1038/sj.bjp.0702935" @default.
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• W2084539802 date "1999-11-01" @default.
• W2084539802 modified "2023-10-18" @default.
• W2084539802 title "Pharmacological activation of the ryanodine receptor in Jurkat T-lymphocytes" @default.
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• W2084539802 doi "https://doi.org/10.1038/sj.bjp.0702935" @default.
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