Kawarabayashi T, Kobayashi M, Akahane M, Ajisawa Y
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan.
Am J Obstet Gynecol. 1996 Nov;175(5):1348-55. doi: 10.1016/s0002-9378(96)70053-4.
Our purpose was to compare the effects of peptidyl and nonpeptidyl oxytocin antagonists on the pregnant rat uterus in relation to the progress of gestation.
Pregnant rats with gestational ages of 17 and 21 days were used. A saturation binding of tritiated oxytocin to myometrial membrane preparation and its displacement by unlabeled oxytocin and the oxytocin antagonists were examined. The inhibitory effects of peptidyl and nonpeptidyl oxytocin on spontaneous, oxytocin-induced, and prostaglandin F2 alpha-induced uterine contractions were also evaluated in vitro in vivo.
The number of tritiated oxytocin binding sites in myometrial membranes of pregnant rats increased markedly at day 21 of gestation compared with day 17 of gestation, whereas the dissociation constants for tritiated oxytocin did not differ significantly. As for the binding affinities to oxytocin receptors of myometrial membranes, the inhibition constant values of nonpeptidyl oxytocin were 79 and 351 times larger than those of peptidyl oxytocin at pregnancy days 17 and 21, respectively. Both drugs remarkably inhibited oxytocin-induced uterine contractions in a dose-dependent manner. However, peptidyl oxytocin did not effect spontaneous and prostaglandin F2 alpha-induced contractions except for spontaneous ones of rats of pregnancy day 21 in vivo. On the other hand, nonpeptidyl oxytocin suppressed spontaneous and prostaglandin F2 alpha-induced contractions of the uterus both in vivo (pregnancy day 17) and in vitro (pregnancy day 21).
These results suggest that peptidyl oxytocin 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 suppressing the contractions. This effect of nonpeptidyl oxytocin may become therapeutically advantageous in clinical application for preterm labor.
我们的目的是比较肽基和非肽基催产素拮抗剂对妊娠大鼠子宫的影响与妊娠进程的关系。
使用妊娠17天和21天的妊娠大鼠。检测氚标记催产素与子宫肌层膜制剂的饱和结合以及未标记催产素和催产素拮抗剂对其的置换作用。还在体内和体外评估了肽基和非肽基催产素对自发、催产素诱导和前列腺素F2α诱导的子宫收缩的抑制作用。
与妊娠第17天相比，妊娠大鼠子宫肌层膜中氚标记催产素结合位点的数量在妊娠第21天显著增加，而氚标记催产素的解离常数无显著差异。至于子宫肌层膜对催产素受体的结合亲和力，非肽基催产素在妊娠第17天和第21天的抑制常数分别比肽基催产素大79倍和351倍。两种药物均以剂量依赖性方式显著抑制催产素诱导的子宫收缩。然而，肽基催产素除了对妊娠第21天大鼠的自发收缩有影响外，对自发和前列腺素F2α诱导的收缩均无作用。另一方面，非肽基催产素在体内（妊娠第17天）和体外（妊娠第21天）均抑制子宫的自发和前列腺素F2α诱导的收缩。
这些结果表明，肽基催产素可能通过在受体部位选择性拮抗催产素作用来抑制子宫收缩，而高浓度的非肽基催产素可能具有直接抑制收缩的额外作用。非肽基催产素的这种作用在早产的临床应用中可能具有治疗优势。
