Properties of amentoflavone, a potent caffeine-like Ca2+ releaser in skeletal muscle sarcoplasmic reticulum.

Abstract Amentoflavone, like caffeine, caused a concentration-dependent increase in Ca 2+ release from the heavy fraction of fragmented sarcoplasmic reticulum of rabbit skeletal muscle. The Ca 2+ -releasing activity of amentoflavone was approximately 20 times more potent than that of caffeine. The bell-shaped profile of Ca 2+ dependence for amentoflavone was almost the same as that for caffeine. Typical blockers of Ca 2+ -induced Ca 2+ release channels, such as Mg 2+ , procaine and ruthenium red, inhibited markedly amentoflavone- and caffeine-induced 45 Ca 2+ release. The maximum 45 Ca 2+ release in response to amentoflavone was not changed by caffeine, but was further increased by adenosine-5′-(β,γ-methylene) triphosphate. This compound enhanced [ 3 H ]ryanodine binding to the heavy fraction of fragmented sarcoplasmic reticulum with a decrease in K D but without a change in B max . These results suggest that amentoflavone, which does not contain a nitrogen atom, probably binds to the caffeine-binding site in Ca 2+ channels and thus potentiates Ca 2+ -induced Ca 2+ release from the heavy fraction of fragmented sarcoplasmic reticulum.