Intracellular calcium mobilization as a target for the spasmolytic action of scopoletin.
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The coumarin scopoletin was isolated in a pure form from the roots of Brunfelsia hopeana Benth. (Solanaceae). In isolated rat aortic rings, scopoletin (26-520 microM) inhibited to approximately the same extent the contractions induced by a variety of substances, including phenylephrine, potassium chloride, serotonin and PGF(2) (alpha). The effect of the coumarin on phenylephrine-induced contractions was not affected by endothelium removal or NO-synthase blockade by L-NAME (100 microM). Scopoletin (78 - 590 microM) antagonized in a concentration-dependent manner (IC(50) = 300 +/- 20 microM, n = 5), transient contractions in Ca(2+)-free media induced by noradrenaline, but not those induced by caffeine. Also, scopoletin did not interfere with the refilling of noradrenaline-sensitive intracellular calcium stores. It is suggested that the non-specific spasmolytic action of scopoletin can be attributed, at least in part, to its ability to inhibit the intracellular calcium mobilization from the noradrenaline-sensitive stores.