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 CaCl(2), with an IC(50) of 1.24 +/- 0.23 x 10(-5) m and 5.94 +/- 0.29 x 10(-5) m, respectively. 14-DAP shifted the CaCl(2) cumulative dose response curve to the right, increasing the EC(50) from 2.08 +/- 0.20 x 10(-4) m to 4.22 +/- 0.22 x 10(-4) m (5 micrometer 14-DAP) and 2.5 +/- 1.0 x 10(-3) m (50 micrometer 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.
Burgos
Rafael A
RA
Institute of Pharmacology, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile. rburgos1@uach.cl
Loyola
Mario
M
Hidalgo
María A
MA
Labranche
Timothy P
TP
Hancke
Juan L
JL
D035685:Andrographis; D000818:Animals; D002122:Calcium Chloride / Q000494:pharmacology*; D015237:Dinoprost; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D020128:Inhibitory Concentration 50; D007545:Isoproterenol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects; D010121:Oxytocin; D010653:Phenylbutazone / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects*; D014638:Vanadates
C114791:14-deoxyandrographolide; D004224:Diterpenes; D010936:Plant Extracts; D014638:Vanadates; D010121:Oxytocin; D015237:Dinoprost; D010653:Phenylbutazone; D007545:Isoproterenol; D002122:Calcium Chloride