Evidence for the mechanism of the inhibitory action of jatrophone in the isolated rat uterine muscle

Gen Pharmacol. 1990;21(1):117-22. doi: 10.1016/0306-3623(90)90605-l.

Abstract

1. Jatrophone (JAT), a diterpene isolated from the plant Jatropha elliptica (1-300 microM), caused a concentration-dependent relaxation effect against acetylcholine (Ach)-oxytocin (Ot)- and KCl-induced uterine sustained contraction. The relative potency order was: Ach greater than Ot greater than KCl. 2. The relaxant effect of JAT was not modified by phorbol ester, forskolin, MIX, TMB-8 and W-7. The increase concentration of calcium (0.2-2 mM) in the medium did not reverse the inhibitory effect caused by JAT. 3. Pre-incubation of the preparations with JAT (16-32 microM) for 20 min, caused a concentration-dependent inhibition of KCl-induced contractile response. At 30 microM, JAT inhibited in an apparently non-competitive manner CaCl2-induced contraction in K+-depolarized preparations. High concentrations of JAT (100 microM) also caused a time-dependent relaxation in CaCl2-induced sustained uterine contraction (T1/2 = approx. 15 min). 4. JAT (30 microM) inhibited the dihydropyridine calcium channel agonist Bay K 8644-induced uterine contraction in an apparently non-competitive fashion, while verapamil (0.1 microM) caused an rightward displacement of Bay K 8644 contraction and marked inhibition of the maximal response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Acetylcholine / pharmacology
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Calcium Channel Blockers
  • Calcium Channels / drug effects
  • Diterpenes / pharmacology*
  • Female
  • In Vitro Techniques
  • Muscle, Smooth / drug effects*
  • Oxytocin / pharmacology
  • Potassium Chloride / pharmacology
  • Rats
  • Uterine Contraction / drug effects
  • Uterus / drug effects

Substances

  • Antineoplastic Agents, Phytogenic
  • Calcium Channel Blockers
  • Calcium Channels
  • Diterpenes
  • jatrophone
  • Oxytocin
  • Potassium Chloride
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • Acetylcholine