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

Amentoflavone, like caffeine, caused a concentration-dependent increase in Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum of rabbit skeletal muscle. The Ca2+-releasing activity of amentoflavone was approximately 20 times more potent than that of caffeine. The bell-shaped profile of Ca2+ dependence for amentoflavone was almost the same as that for caffeine. Typical blockers of Ca2+-induced Ca2+ release channels, such as Mg2+, procaine and ruthenium red, inhibited markedly amentoflavone- and caffeine-induced Ca-45(2+) release. The maximum Ca-45(2+) release in response to amentoflavone was not changed by caffeine, but was further increased by adenosine-5'-(beta,gamma-methylene) triphosphate. This compound enhanced [H-3]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 Ca2+ channels and thus potentiates Ca2+-induced Ca2+ release from the heavy fraction of fragmented sarcoplasmic reticulum. (C) 1999 Elsevier Science B.V. All rights reserved.