Calcium-dependent effect of Tricolorin A on intestinal and arterial smooth muscle contractility

In this study we report the effect of Tricolorin A, a resin glycoside isolated from the plant Ipomoea tricolor Cav. (Convolvulaceae), on intestinal and arterial smooth muscle contractility. This compound elicited a concentration-dependent stimulation of spontaneous contractions of the guinea pig ileum (EC₅₀=6.99±1.08µg/ml) and a concentration-dependent vasorelaxation of isolated intact rat aorta (EC₅₀=4.63±1.1µg/ml). Both effects were completely abolished in the absence of extracellular Ca²⁺. Verapamil (1µM), an L-type voltage-dependent Ca²⁺ channel blocker, significantly inhibited the contractile response produced by Tricolorin A on the ileum. However, this blocker did not affect the vasodilatory action of this compound. Our findings suggest that the contractions induced by Tricolorin A on the ileum are caused mainly by an increase in Ca²⁺ permeability that occurs through L-type voltage-dependent Ca²⁺ channels found in the cell membrane of the smooth muscle. On the other hand, our results indicate that the influx of Ca²⁺ through L-type voltage-dependent Ca²⁺ channels does not participate prominently in the vasorelaxant effect elicited by Tricolorin A. Vascular relaxation induced by Tricolorin A was endothelium-dependent and significantly decreased in the presence of nitric oxide synthase (NOS) and soluble guanylate cyclase inhibitors, and a NO scavenger. These results suggest that the vasodilatation produced by Tricolorin A is mainly due to activation of the NO/cGMP pathway, which results from an increased influx of extracellular Ca²⁺ into the endothelial cells.