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

Abstract

1. 1. Jatrophone (JAT), a diterpene isolated from the plant Jatropha elliptica (1–300 μM), caused a concentration-dependent relaxation effect against acetylcholine (Ach)-oxytocin (Ot)- and KCl-induced uterine sustained contraction. The relative potency order was: Ach > Ot > KCl. 2. 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. 3. Pre-incubation of the preparations with JAT (16–32 μM) for 20 min, caused a concentration-dependent inhibition of KCl-induced contractile response. At 30 μM, JAT inhibited in an apparently non-competitive manner CaCl 2-induced contraction in K +-depolarized preparations. High concentrations of JAT (100 μM) also caused a time-dependent relaxation in CaCl 2-induced sustained uterine contraction ( T 1 2 = approx. 15 min ). 4. 4. JAT (30 μM) inhibited the dihydropyridine calcium channel agonist Bay K 8644-induced uterine contraction in an apparently non-competitive fashion, while verapamil (0.1 μM) caused in rightward displacement of Bay K 8644 contraction and marked inhibition of the maximal response.