Bisprasin, a novel Ca2+ releaser with caffeine-like properties from a marine sponge, Dysidea spp., acts on Ca2+-induced Ca2+ release channels of skeletal muscle sarcoplasmic reticulum

Bisprasin, a unique bromotyrosine derivative containing a disulfide linkage , was isolated from a marine sponge of Dysidea spp. This compound caused a concentration-dependent (from 10 to 30 mu M) increase in the Ca-45(2+) rele ase from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR) of rabbit skeletal muscle in the same way as does caffeine. The 50% effect ive concentrations of bisprasin and caffeine were approximately 18 mu M and 1.2 mM, respectively, indicating that the Ca-45(2+)-releasing activity of bisprasin was approximately 70 times more potent than that of caffeine in H SR. The bell-shaped profile of Ca2+ dependence for bisprasin was almost the same as that for caffeine. Typical blockers of Ca2+-induced Ca2+ release c hannels, such as Mg2+, procaine, and ruthenium red, inhibited markedly bisp rasin- and caffeine-induced Ca-45(2+) release from HSR. This compound, like caffeine, significantly enhanced [H-3] ryanodine binding to HSR. Scatchard analysis of [H-3] ryanodine binding to HSR revealed that bisprasin and caf feine 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 [H-3] ryanodine binding w ere further enhanced by adenosine-5'-(beta, gamma-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 bis prasin, which, like caffeine, induces Ca2+ release from skeletal muscle SR mediated through the ryanodine receptor.