Mechanisms involved in the effects of phenidone, diclofenac and ethacrynic acid in rat uterus in vitro.
1. The effects of phenidone (P, 10(-4)-10(-3) M), sodium diclofenac (D, 10(-5)-10(-4) M) and ethacrynic acid (E, 10(-5)-10(-4) M), proposed as inhibitors of eicosanoid synthesis, on the contractions of rat uterus induced by several agonists have been studied. 2. P, D and E inhibit the motility induced by oxytocin (4 mU/ml) (IC50: 4.62 x 10(-4), 2.55 x 10(-4) and 2.98 x 10(-5) M, respectively). 3. P (10(-3) M), D (10(-4) M) and E (10(-4) M) also inhibit the contraction induced by methacholine (10(-5) M), prostaglandin F2a (10(-6) M) and CaCl2 (6 mM), and relaxed, in a dose-dependent way, the tonic component of contraction to KCl (60 mM) (IC50: 5.81 x 10(-4), 6.67 x 10(-5) and 7.55 x 10(-5) M, respectively). 4. The CaCl2 (0.1-10 mM) reverted the relaxation of KCl contraction produced by P, but not by D or E. None of the inhibitions on CaCl2 (6 mM) are reverted by Bay K 8644. 5. D and E also relaxed the tonic contraction to vanadate (10(-4) M) in uterus incubated in calcium free solution P, enhances the vanadate-induced contractions.
Pérez Vallina
J R
JR
Laboratorio de Farmacología (Departamento de Medicina), Universidad de Oviedo, Spain.
Cantabrana
B
B
Hidalgo
A
A
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002122:Calcium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008688:Methacholine Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010121:Oxytocin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects*; D014638:Vanadates / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016859:Lipoxygenase Inhibitors; D008688:Methacholine Compounds; D011720:Pyrazoles; D004008:Diclofenac; D014638:Vanadates; D010121:Oxytocin; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004492:Edetic Acid; D015237:Dinoprost; C015429:phenidone; D002122:Calcium Chloride; D004976:Ethacrynic Acid; D002118:Calcium