TY - JOUR T1 - Xestoquinone, Isolated from Sea Sponge, Causes Ca<sup>2+</sup>Release through Sulfhydryl Modification from Skeletal Muscle Sarcoplasmic Reticulum JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 976 LP - 981 VL - 291 IS - 3 AU - Masaaki Ito AU - Yutaka Hirata AU - Hideshi Nakamura AU - Yasushi Ohizumi Y1 - 1999/12/01 UR - http://jpet.aspetjournals.org/content/291/3/976.abstract N2 - Xestoquinone (XQN) (3 × 10−7 to 3 × 10−3 M), isolated from the sea sponge Xestospongia sapra, induced a concentration-dependent Ca2+release from the heavy fraction of fragmented sarcoplasmic reticulum (HSR) of rabbit skeletal muscle with an EC50 value of ∼30 μM. On the basis of the EC50, XQN is 10 times more potent than caffeine. Dithiothreitol completely blocked XQN-induced Ca2+ release from HSR without affecting that induced by caffeine. Caffeine-induced Ca2+ release was reduced markedly by Mg2+, procaine, and ruthenium red, agents that are known to block release of Ca2+ from sarcoplasmic reticulum, whereas that induced by XQN was not inhibited. The bell-shaped profile of Ca2+ dependence for XQN was significantly shifted upward in a wider range of pCa (between 7 and 3), whereas that for caffeine was shifted to the left in a narrower range of pCa (between 8 and 7). The maximum response to caffeine in45Ca2+ release was not affected by 9-methyl-7-bromoeudistomin D, whereas the response was further increased by XQN. XQN caused a concentration-dependent decrease in [3H]ryanodine binding to HSR. This effect of XQN also was abolished in the presence of dithiothreitol. Scatchard analysis revealed that the mode of inhibition by XQN was noncompetitive in [3H]ryanodine binding to HSR. These results indicate that sulfhydryl groups are involved in both the XQN effect on ryanodine binding and on Ca2+ release. The American Society for Pharmacology and Experimental Therapeutics ER -