RESUMEN
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 (pD2' 4.12 +/- 0.09) similar to verapamil (pD2' 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 x 10(-5) M) and the standard agent sodium nitroprusside (IC50 1.9 x 10(-8) M). In Ca(2+)-free medium, the alkaloid reduced the intracellular Ca(2+)-dependent transient contraction to noradrenaline by inhibiting the release of Ca2+ (IC50 2.6 x 10(-5) M) from the stores and the refilling (IC50 1.9 x 10(-5) M) of the intracellular stores. The standard agent, procaine, also inhibited the release of Ca2+ (IC50 3.2 x 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 x 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.