Drug-induced Ca2+ release from isolated sarcoplasmic reticulum. II. Releases involving a Ca2+-induced Ca2+ release channel.
1987; Elsevier BV; Volume: 262; Issue: 13 Linguagem: Inglês
10.1016/s0021-9258(18)45549-4
ISSN1083-351X
Autores Tópico(s)Neuroscience and Neuropharmacology Research
ResumoCalcium ions that have been preloaded into isolated sarcoplasmic reticulum subfractions in the presence of ATP and pyrophosphate may be released upon addition of a large number of diverse pharmacologic substances.We report here that not only caffeine, but also Ca2+ ions, thymol, quercetin, menthol, halothane, chloroform, l-ethyl-2-methylbenzimidazole9 ryanodine, tetraphenylboron, ketoconazole, miconazole, clotrimazole, W-7, doxorubicin, 5,5'-dithiobis-(Z-nitrobenzoic acid), p-chloromercuribenzoic acid, and low concentrations of Ag+ induce Ca2+ release from such triadic sarcoplasmic reticulum.All these drugs induce increased unidirectional Ca2+ efflux.We believe all these drug-induced Ca2+ releases are mediated by Ca2+ efflux through the same ion channel since 1) these releases are all greatly attenuated when light sarcoplasmic reticulum is substituted for triads and are even more pronounced when transverse tubule-free terminal cisternae are substituted for triads, and 2) all these forms of drug-induced Ca2+ release are inhibited by submicromolar concentrations of ruthenium red, and 3) by submillimolar concentrations of tetracaine, 4) 9aminoacridine, and 5) Ba2+, yet they are not affected by nifedipine even at a concentration of 50 p ~.A very large number of chemically diverse substances have been reported to release calcium from isolated sarcoplasmic reticulum or from SR' of skinned skeletal muscle fibers.In addition to caffeine (1-3), these substances include Ca2+ itself (4-7), thymol (2, 8), quercetin (9-11), halothane (12-14), ryanodine (15-18), tetraphenylboron (19), ketoconazole (ZO), doxorubicin (X), and Ag+ (22, 23).The chemical diversity of these substances appears to make it unlikely that they would all cause Ca'+ release by the same mechanism or through the same efflux pathway.We have attempted to address this issue by examining the distribution of Ca2+ release activity among several SR subfractions and by assessing the ability of several reputed SR Ca2+ channel blockers to inhibit the releases under study.Using these criteria, we have found evidence (24) that some substances not considered here cause Ca2+ to be released
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