The inhibitory effects of frusemide on Ca2+ influx pathways associated with oxytocin-induced contractions of rat myometrium.
Contractile responses induced by 25 mumol/l oxytocin in myometrial strips isolated from the uterus of estradiol-dominated rats comprised both phasic and tonic components. In a Ca(2+)-free medium (containing 0.1 mmol/l EGTA and no added Ca2+), the oxytocin-induced contractions seemed to be associated with Ca2+ release from intracellular stores. Frusemide, known to lower the cAMP level in the rat myometrium, did not affect the responses due to Ca2+ release but inhibited those mediated through an acceleration of the Ca2+ influx. The permanent presence of frusemide (1.5 mmol/l) in the CaCl2-containing medium influenced the oxytocin-induced responses in the same manner as did omission of Ca2+ from the medium. The frusemide-sensitive component of the responses to oxytocin was superimposed on a persistent contraction caused by KCl depolarization, 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. This decrease varied with the frusemide concentration, and could be partly prevented by addition of dibutyryl-cAMP; i.e. probably, it was mediated 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 mumol/l) both voltage-gated and receptor-operated Ca2+ entries are regulated by cAMP-dependent protein kinases.
Mozhayeva
M G
MG
Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St.Petersburg, Russia.
Bagrov YaYu
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism*; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014590:Uterine Contraction / Q000187:drug effects* / Q000502:physiology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D010121:Oxytocin; D003994:Bucladesine; D005665:Furosemide; D014700:Verapamil; D000242:Cyclic AMP; D002118:Calcium