Dual Effect of Suramin on Calcium Fluxes Across Sarcoplasmic

Suramin is a polysulfonated naphthlyurea developed originally to treat trypanosomiasis. This drug has gained considerable atten-tion recently as an effective anticancer agent. Previous studies have demonstrated that suramin also is an antagonist of ATP at P2 punnergic receptors. In the present study suramin was shown to evoke Ca release from skeletal muscle sarcoplasmic retic-ulum (SR) vesicles in a concentration-dependent manner. Ca release was inducable from vesicles derived from junctional SR but not from those derived from longitudinal SR. This subcellular site-dependent specificity suggests that suramin’s actions on muscle involve the Ca release channel (CRC), a protein unique to terminal cistemae. This channel has been established as the site of action of ryanoid alkaloids such as ryanodine and dehy-droryanodine. Suramin did not mimic ryanoid actions on the SR CRC, nor did it competitively diminish ryanodine binding. Instead