title: Properties of amentoflavone, a potent caffeine-like Ca2+ releaser in skeletal muscle sarcoplasmic reticulum.
abstract: 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 45Ca2+ release. The maximum 45Ca2+ release in response to amentoflavone was not changed by caffeine, but was further increased by adenosine-5'-(beta,gamma-methylene) triphosphate. This compound enhanced [3H]ryanodine binding to the heavy fraction of fragmented sarcoplasmic reticulum with a decrease in K(D) but without a change in Bmax. 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.
authors.affiliation: Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Y
authors.initials: Y
authors.lastname: Mimaki
authors.forename: Y
authors.initials: Y
authors.lastname: Sashida
authors.forename: Y
authors.initials: Y
authors.lastname: Ohizumi
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044946:Biflavonoids; D001667:Binding, Competitive / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004566:Electrodes; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D012433:Ryanodine / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D014316:Tritium
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D044946:Biflavonoids; D005419:Flavonoids; D014316:Tritium; D012433:Ryanodine; D002110:Caffeine; C011164:amentoflavone; D002118:Calcium