4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol

Mariann Skaliczki, Balázs Lukács, Zsuzsanna Magyar, Tünde Kovács, Miklós Bárdi, Szabolcs Novák, Gyula Diszházi, Sándor Sárközi, Ildikó Márton, Judit Péli-Szabó, István Jóna, Péter Nánási, János Almássy

Research output: Contribution to journalArticle

Abstract

In this study we performed the comprehensive pharmacological analysis of two stereoisomers of 4-chloro-meta-cresol (4CMC), a popular ryanodine receptor (RyR) agonist used in muscle research. Experiments investigating the Ca2+-releasing action of the isomers demonstrated that the most potent isomer was 4-chloro-orto-cresol (4COC) (EC50 = 55 ± 14 μM), although 3-chloro-para-cresol (3CPC) was more effective, as it was able to induce higher magnitude of Ca2+ flux from isolated terminal cisterna vesicles. Nevertheless, 3CPC stimulated the hydrolytic activity of the sarcoplasmic reticulum ATP-ase (SERCA) with an EC50 of 91 ± 17 μM, while 4COC affected SERCA only in the millimolar range (IC50 = 1370 ± 88 μM). IC50 of 4CMC for SERCA pump was 167 ± 8 μM, indicating that 4CMC is not a specific RyR agonist either, as it activated RyR in a similar concentration (EC50 = 121 ± 20 μM). Our data suggest that the use of 4COC might be more beneficial than 4CMC in experiments, when Ca2+ release should be triggered through RyRs without influencing SERCA activity.

Original languageEnglish
Article number102213
JournalCell Calcium
Volume88
DOIs
Publication statusPublished - Jun 2020

Keywords

  • 3-chloro-para-cresol
  • 4-chloro-meta-cresol
  • Chloro-orto-cresol
  • Ryanodine receptor
  • SERCA
  • Skeletal muscle

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of '4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol'. Together they form a unique fingerprint.

  • Cite this

    Skaliczki, M., Lukács, B., Magyar, Z., Kovács, T., Bárdi, M., Novák, S., Diszházi, G., Sárközi, S., Márton, I., Péli-Szabó, J., Jóna, I., Nánási, P., & Almássy, J. (2020). 4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol. Cell Calcium, 88, [102213]. https://doi.org/10.1016/j.ceca.2020.102213