Abstract

Bisprasin, a unique bromotyrosine derivative containing a disulfide linkage, was isolated from a marine sponge of Dysideaspp. This compound caused a concentration-dependent (from 10 to 30 μM) increase in the ⁴⁵Ca²⁺ release from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR) of rabbit skeletal muscle in the same way as does caffeine. The 50% effective concentrations of bisprasin and caffeine were approximately 18 μM and 1.2 mM, respectively, indicating that the⁴⁵Ca²⁺-releasing activity of bisprasin was approximately 70 times more potent than that of caffeine in HSR. The bell-shaped profile of Ca²⁺ dependence for bisprasin was almost the same as that for caffeine. Typical blockers of Ca²⁺-induced Ca²⁺ release channels, such as Mg²⁺, procaine, and ruthenium red, inhibited markedly bisprasin- and caffeine-induced ⁴⁵Ca²⁺ release from HSR. This compound, like caffeine, significantly enhanced [³H]ryanodine binding to HSR. Scatchard analysis of [³H]ryanodine binding to HSR revealed that bisprasin and caffeine decreased the K_D value without affecting the B_max value, suggesting that both the drugs facilitate the opening of ryanodine receptor channels. The bisprasin- and caffeine-induced increases in [³H]ryanodine binding were further enhanced by adenosine-5′-(β,γ-methylene)triphosphate. These results suggest that the pharmacological properties of bisprasin are almost similar to those of caffeine, except for its 70-fold higher potency. Here, we present the first report on the pharmacological properties of bisprasin, which, like caffeine, induces Ca²⁺ release from skeletal muscle SR mediated through the ryanodine receptor.