Evidence for the mechanism of the inhibitory action of jatrophone in the isolated rat uterine muscle.
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.
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
J B
JB
Calixto
A E
AE
Sant'ana
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002121:Calcium Channel Blockers; D015220:Calcium Channels / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects*; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004224:Diterpenes; C006386:jatrophone; D010121:Oxytocin; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000109:Acetylcholine