Modification of Ca2+ Metabolism in the Rabbit Aorta as a Mechanism of Spasmolytic Action of Warifteine, a Bisbenzylisoquinoline Alkaloid Isolated from the Leaves of Cissampelos sympodialis Eichl. (Menispermaceae)

Journal of Pharmacy and Pharmacology - Tập 48 Số 3 - Trang 332-336 - 2011
Maria Regina de Freitas1, Steyner F. Côrtes1, George Thomas1, José Maria Barbosa‐Filho1
1Laboratório de Technologia Farmacêutica, Universidade Federal de Paraíba, Caixa Postal 5009, CEP 58051-970, Joaò Pessoa, PB, Brazil

Tóm tắt

Abstract The regulation of intracellular Ca2+ as a mechanism of spasmolytic activity of a bisbenzylisoquinoline alkaloid, warifteine, isolated from the leaves of Cissampelos sympodialis, Eichl (Menispermaceae) was studied in the rabbit aorta. Warifteine (pD'2 4.12 ± 0.09) similar to verapamil (pD'2 6.89 · 0.05) antagonized, in a noncompetitive and reversible manner, KCl-induced contractions, mediated by Ca2+ entry through voltage-operated channels. Noradrenaline-induced sustained contractions mediated by Ca2+ entry through receptor-operated channels were also inhibited by warifteine (IC50 6.03 × 10−5 m) and the standard agent sodium nitroprusside (IC50 1.9 × 10−8 m). In Ca2+-free medium, the alkaloid reduced the intracellular Ca2+-dependent transient contraction to noradrenaline by inhibiting the release of Ca2+ (IC50 2.6 × 10−5 m) from the stores and the refilling (IC50 1.9 × 10−5 m) of the intracellular stores. The standard agent, procaine, also inhibited the release of Ca2+ (IC50 3.2 × 10−5 m) but had no significant effect on Ca2+ uptake into the stores. Warifteine failed to affect intracellular Ca2+ stores sensitive to caffeine, while procaine inhibited (IC50 7.9 × 10−4 m) the release of Ca2+ from these stores. The results indicate that warifteine may cause muscle relaxation by inhibiting Ca2+ channels and by modifying the intracellular Ca2+ stores sensitive to noradrenaline.

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Journal of Pharmacy and Pharmacology

Tập 48 Số 3

332-336

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