Abstract

1. 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. 2. 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. 3. 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. 4. Sanguinarine altered [ 3H]-ryanodine binding to the RyR of isolated SR vesicles, potentiating [ 3H]-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.

Original languageEnglish
Pages (from-to)299-306
Number of pages8
JournalBritish Journal of Pharmacology
Volume130
Issue number2
Publication statusPublished - 2000

Fingerprint

Sarcoplasmic Reticulum
Contracture
Skeletal Muscle
Calcium
Ryanodine Receptor Calcium Release Channel
Ryanodine
Dithiothreitol
Diaphragm
Ruthenium Red
Phrenic Nerve
Calcium Channels
Nifedipine
sanguinarine
Alkaloids
Muscles

Keywords

  • Contracture
  • Ryanodine receptor
  • Sanguinarine
  • Skeletal muscle

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{52de4f67e2f740fea6ff95549cb4b15a,
title = "Induction of skeletal muscle contracture and calcium release from isolated sarcoplasmic reticulum vesicles by sanguinarine",
abstract = "1. 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. 2. 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. 3. 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. 4. Sanguinarine altered [ 3H]-ryanodine binding to the RyR of isolated SR vesicles, potentiating [ 3H]-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.",
keywords = "Contracture, Ryanodine receptor, Sanguinarine, Skeletal muscle",
author = "Hu, {C. M.} and Cheng, {H. W.} and Cheng, {Y. W.} and Kang, {J. J.}",
year = "2000",
language = "English",
volume = "130",
pages = "299--306",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "John Wiley and Sons Inc.",
number = "2",

}

TY - JOUR

T1 - Induction of skeletal muscle contracture and calcium release from isolated sarcoplasmic reticulum vesicles by sanguinarine

AU - Hu, C. M.

AU - Cheng, H. W.

AU - Cheng, Y. W.

AU - Kang, J. J.

PY - 2000

Y1 - 2000

N2 - 1. 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. 2. 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. 3. 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. 4. Sanguinarine altered [ 3H]-ryanodine binding to the RyR of isolated SR vesicles, potentiating [ 3H]-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.

AB - 1. 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. 2. 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. 3. 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. 4. Sanguinarine altered [ 3H]-ryanodine binding to the RyR of isolated SR vesicles, potentiating [ 3H]-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.

KW - Contracture

KW - Ryanodine receptor

KW - Sanguinarine

KW - Skeletal muscle

UR - http://www.scopus.com/inward/record.url?scp=0034061833&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034061833&partnerID=8YFLogxK

M3 - Article

C2 - 10807666

AN - SCOPUS:0034061833

VL - 130

SP - 299

EP - 306

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 2

ER -