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Induction of skeletal muscle contracture and calcium release from isolated sarcoplasmic reticulum vesicles by sanguinarine
Author(s) -
Hu C M,
Cheng H W,
Cheng Y W,
Kang J J
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703279
Subject(s) - sanguinarine , ryanodine receptor , ruthenium red , chelerythrine , calcium , chemistry , endoplasmic reticulum , dithiothreitol , vesicle , biophysics , muscle contraction , biochemistry , endocrinology , biology , alkaloid , membrane , stereochemistry , enzyme , organic chemistry , protein kinase c
The benzophenanthrine alkaloid, sanguinarine, was studied for its effects on isolated mouse phrenic‐nerve diaphragm preparations. Sanguinarine induced direct, dose‐dependent effects on muscle contractility. Sanguinarine‐induced contracture was partially inhibited when the extracellular Ca 2+ was removed or when the diaphragm was pretreated with nifedipine. Depletion of sarcoplasmic reticulum (SR) internal calcium stores completely blocked the contracture. Sanguinarine induced Ca 2+ release from the actively loaded SR vesicles was blocked by ruthenium red and dithiothreitol (DTT), consistent with the ryanodine receptor (RyR) as the site of sanguinarine action. Sanguinarine altered [ 3 H]‐ryanodine binding to the RyR of isolated SR vesicles, potentiating [ 3 H]‐ryanodine binding at lower concentrations and inhibiting binding at higher concentrations. All of these effects were reversed by DTT, suggesting that sanguinarine‐induced Ca 2+ release from SR occurs through oxidation of critical SH groups of the RyR SR calcium release channel.British Journal of Pharmacology (2000) 130 , 299–306; doi: 10.1038/sj.bjp.0703279