Characterization of increased Ca2+ efflux by quercetin from the sarcoplasmic reticulum in frog skinned skeletal muscle fibres.
To clarify further the characteristics of the Ca-releasing action of quercetin, we examined the effect of quercetin on Ca2+ efflux from the sarcoplasmic reticulum without Ca uptake activity by omission of ATP in the presence of a high concentration (10 mM EGTA) of Ca2+ buffer, using mechanically skinned fibres from frog skeletal muscles. Quercetin increases the rate of Ca release in the presence of Ca2+ and shifts the relationship between Ca2+ concentration and the rate of Ca release to a lower range of Ca2+ concentrations. AMP potentiates the effect of quercetin. Mg2+ and procaine decrease the rate of Ca release in the presence of quercetin. These findings indicate that quercetin is very similar to caffeine; in fact, experiments confirmed that quercetin shares the site(s) of action with caffeine. Subsequent findings, however, suggest that the mechanism of the drug-induced Ca release is not as simple as expected with caffeine which may increase the affinity for Ca2+ of the 'Ca2+-induced Ca-release' mechanism, and that drugs, Ca2+ and nucleotide interact with one another in a more complex way to open the gate for Ca release. In the presence of 10 mM EGTA quercetin also causes Ca release in the virtual absence of Ca2+ if a sufficient amount of AMP is present, and the rate of Ca release in the presence of 1.55 micron Ca2+ showed different dependence on AMP concentration with and without quercetin. A higher concentration of Mg2+ is required in the presence of AMP than in the absence of AMP in order to eliminate Ca release by quercetin.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D009132:Muscles / Q000378:metabolism; D011343:Procaine / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology*; D011898:Ranidae; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D005419:Flavonoids; D002110:Caffeine; D000249:Adenosine Monophosphate; D011343:Procaine; D004533:Egtazic Acid; D011794:Quercetin; D008274:Magnesium; D002118:Calcium