4-chloro-orto-cresol activates ryanodine receptor more selectively and potently than 4-chloro-meta-cresol
| Autor: | Gyula Diszházi, Zsuzsanna Magyar, Balázs András Lukács, Tünde Kovács, János Almássy, Mariann Skaliczki, Péter P. Nánási, Judit Péli-Szabó, Ildikó Márton, Istvan Jona, Szabolcs Novák, Miklós Bárdi, Sándor Sárközi |
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| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
Agonist SERCA Physiology medicine.drug_class Sarcoplasmic Reticulum Calcium-Transporting ATPases Cresols Caffeine Microsomes medicine Animals Terminal cisternae Molecular Biology IC50 Adenosine Triphosphatases Ions Chemistry Ryanodine receptor Endoplasmic reticulum Vesicle Hydrolysis Skeletal muscle Ryanodine Receptor Calcium Release Channel Stereoisomerism Cell Biology Sarcoplasmic Reticulum medicine.anatomical_structure cardiovascular system Biophysics Calcium Rabbits tissues Ion Channel Gating Muscle Contraction |
| Zdroj: | Cell calcium. 88 |
| ISSN: | 1532-1991 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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