COMPARISON OF IN-VITRO AND IN-VIVO INHIBITORY EFFECTS OF PEPTIDE AND NONPEPTIDE OXYTOCIN ANTAGONISTS ON RADIOLIGAND BINDING AND UTERINE CONTRACTILITY OF RATS DURING PREGNANCY

OBJECTIVE: Our purpose was to compare the effects of peptidyl and nonp eptidyl oxytocin antagonists on the pregnant rat uterus in relation to the progress of gestation. STUDY DESIGN: Pregnant rats with gestation al ages of 17 and 21 days were used. A saturation binding of tritiated oxytocin to myometrial membrane preparation and its displacement by u nlabeled oxytocin and the oxytocin antagonists were examined. The inhi bitory effects of peptidyl and nonpeptidyl oxytocin on spontaneous, ox ytocin-induced, and prostaglandin F-2 alpha-induced uterine contractio ns were also evaluated in vitro and in vivo. RESULTS: The number of tr itiated oxytocin binding sites in myometrial membranes of pregnant rat s increased markedly at day 21 of gestation compared with day 17 of ge station, whereas the dissociation constants for tritiated oxytocin did not differ significantly As for the binding affinities to oxytocin re ceptors of myometrial membranes, the inhibition constant values of non peptidyl oxytocin were 79 and 351 times larger than those of peptidyl oxytocin at pregnancy days 17 and 21, respectively. Both drugs remarka bly inhibited oxytocin-induced uterine contractions in a dose-dependen t manner, However, peptidyl oxytocin did not affect spontaneous and pr ostaglandin F-2 alpha-induced contractions except for spontaneous ones of rats of pregnancy day 21 in vivo. On the other hand, nonpeptidyl o xytocin suppressed spontaneous and prostaglandin F-2 alpha-induced con tractions of the uterus both in vivo (pregnancy day 17) and in vitro ( pregnancy day 21). CONCLUSION: These results suggest that peptidyl oxy tocin may inhibit uterine contractions by selectively antagonizing the oxytocin action at the receptor site, whereas nonpeptidyl oxytocin at high concentrations may have the additional effect of directly suppre ssing the contractions. This effect of nonpeptidyl oxytocin may become therapeutically advantageous in clinical application for preterm labo r.