Effect of 14-deoxyandrographolide on calcium-mediated rat uterine smooth muscle contractility

In this study, the effect of 14-deoxyandrographolide (14-DAP) on calcium channel-dependent rat uterine smooth muscle contraction was evaluated. Using a tissue bath preparation, 14-DAP was able to reduce the contractile response to 0.3 and 3.0 mM of CaCl2, with an IC50 of 1.24 +/- 0.23 x 10(-5) M and 5.94 +/- 0.29 x 10(-5) M, respectively. 14-DAP shifted the CaCl2 cumulative dose response curve to the right, increasing the EC50 from 2.08 +/- 0.20 x 10(-4) M to 4.22 +/- 0.22 x 10(-4) M (5 muM 14-DAP) and 2.5 +/- 1.0 x 10(-3) M (50 muM 14-DAP). In order to determine if 14-DAP had any effect on intracellular calcium, the relaxant response to 14-DAP following contraction by oxytocin, PGF(2alpha) and vanadate in Ca+2-free solution was compared with that of isoproterenol and phenylbutazone. While isoproterenol and phenylbutazone relaxed the smooth muscle in a dose-dependent manner, 14-DAP did not have any effect on either the oxytocin, PGF(2alpha) or vanadate-induced smooth muscle contraction. Based on these data, it appears that 14-DAP is an uterine smooth muscle relaxant which produces a selective blockade of voltage operated calcium channels. Copyright (C) 2003 John Wiley Sons, Ltd.