Abstract
Quinolidomicin A 1, a 60-membered macrolide purified from an actinomycete Micromonospora sp. markedly induced 45Ca 2+ release from the heavy fraction of skeletal muscle sarcoplasmic reticulum (HSR), but induced only slightly from the light fraction of sarcoplasmic reticulum (LSR), showing a lack of the i onophoretic activity even at high concentration (300 μM). This was also confirmed by measuring the 45Ca 2+ transport activity of quinolidomicin A 1 across an organic solvent barrier. Quinolidomicin A 1 (3–300 μM) increased 45Ca 2+ release from HSR with an EC 50 value of approx. 20 μM. The potency of quinolidomicin A 1 was approx. 100-fold higher than that of caffeine. The bell-shaped profile of Ca 2+ dependence for quinolidomicin A 1 was different from that for caffeine. Blockers of Ca 2+ release channels such as Mg 2+ (10 mM), procaine (10 mM) and ruthenium red (10 μM) partially blocked quinolidomicin A 1 (30 μM)-induced 45Ca 2+ release from HSR. At 0°C, quinolidomicin A 1-induced 45Ca 2+ release was ascertained not to be due to the inhibition of Ca 2+ ATPase by the ATPase assay. Quinolidomicin A 1 potentiated [ 3H]ryanodine binding to HSR with a decrease in K D but without a change in B max. These result suggest that quinolidomicin A 1-induced Ca 2+ release from HSR is consisted of two components, which are both sensitive and insensitive to blockers of Ca 2+ release channels, and that the former component is associated with the ryanodine receptor.
Published Version
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