A Ca 2+ channel blocker-like effect of dehydrocurdione on rodent intestinal and vascular smooth muscle

Abstract

Effects of dehydrocurdione, a zedoary-derived sesquiterpene, on smooth muscle were investigated by recording the mechanical activity of intestines and aorta from guinea pigs and rats. Dehydrocurdione (0.1–3 mM) induced a sustained relaxation of rat duodenum and inhibited spontaneous motility. Dehydrocurdione (0.1–1 mM) inhibited the contractile response of guinea pig ileum induced by acetylcholine (0.01–10 μM), histamine (0.03–10 μM) and substance P (0.1–30 nM) in a non-competitive manner. Acetylcholine (0.5 μM) elicited a transient contraction followed by a sustained contraction of guinea pig ileum, and dehydrocurdione pretreatment inhibited the sustained component, which depends on Ca 2+ entry from the extracellular space. The high K +-induced contraction of rat aortic ring is reported to be blocked by Ca 2+ channel blockers, while the norepinephrine-induced contraction includes a Ca 2+ channel blocker-resistant component. Dehydrocurdione (1 mM) blocked the high K + (60 mM)-induced contraction of rat aortic ring by 81%, while it inhibited the norepinephrine (1 μM)-induced contraction by only 28%. Dehydrocurdione (1 mM) significantly reduced the high K +-stimulated increase in cytosolic Ca 2+ level of Fura-2-loaded mesenteric artery from rats. These results suggest that the inhibitory effects of dehydrocurdione on intestinal and vascular smooth muscle are mediated by blockade of Ca 2+ entry from the extracellular space.