THE INHIBITORY EFFECTS OF FRUSEMIDE ON CA2-INDUCED CONTRACTIONS OF RAT MYOMETRIUM( INFLUX PATHWAYS ASSOCIATED WITH OXYTOCIN)

Contractile responses induced by 25 mu mol/l oxytocin in myometrial st rips isolated from the uterus of estradiol-dominated rats comprised bo th phasic and tonic components. In a Ca2+-free medium (containing 0.1 mmol/l EGTA and no added Ca2+), the oxytocin-induced contractions seem ed to be associated with Ca2+ release from intracellular stores. Fruse mide, known to lower the cAMP level in the rat myometrium, did not aff ect the responses due to Ca2+ release but inhibited those mediated thr ough an acceleration of the Ca2+ influx. The permanent presence of fru semide (1.5 mmol/l) in the CaCl2-containing medium influenced the oxyt ocin-induced responses in the same manner as did omission of Ca2+ from the medium. The frusemide-sensitive component of the responses to oxy tocin was superimposed on a persistent contraction caused by KCl depol arization, suggesting that frusemide completely inhibited the oxytocin -induced Ca2+ influx. At the same time, frusemide moderately (by only 34 +/- 7%) decreased the amplitude of the KCl-induced contracture. Thi s decrease varied with the frusemide concentration, and could be partl y prevented by addition of dibutyryl-cAMP; i.e. probably, it was media ted by an inhibition of voltage-gated Ca2+ influx due to a decrease in the intracellular cAMP level. The data presented seem to suggest that in the rat myometrium exposed to oxytocin (25 mu mol/l) both voltage- gated and receptor-operated Ca2+ entries are regulated by cAMP-depende nt protein kinases.