Abstract

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 × 10-5 M and 5.94 ± 0.29 × 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 ?m 14-DAP) and 2.5 ± 1.0 × 10-3 M (50 ?M 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, PGF2? 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, PGF2? 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 © 2003 John Wiley & Sons, Ltd.