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 KD value without affecting the Bmax 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.
Footnotes
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Send reprint requests to: Yasushi Ohizumi, Ph.D., Department of Pharmaceutical Molecular Biology, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan. E-mail: ohizumi{at}mail.pharm.tohoku.ac.jp
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↵1 This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan.
- Abbreviations:
- SR
- sarcoplasmic reticulum
- HSR
- heavy fraction of fragmented skeletal muscle sarcoplasmic reticulum
- LSR
- light fraction of fragmented skeletal muscle sarcoplasmic reticulum
- MBED
- 9-methyl-7-bromoeudistomin D
- MOPS
- 3-(N-morpholino)propanesulfonic acid
- AMP-PCP
- adenosine-5′-(β,γ-methylene)triphosphate
- Received June 25, 1999.
- Accepted November 9, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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