Theffects' in vivo of acetorphan, an _enkephalinase inhibitor and naloxone, an opiate antagonist on the - - oxytocin- induced myometrial mechanical activity were studied at day 21 of pregnancy in rats. Acetarpban" I 10 mg kg -1 (i.v.) increased (344%) spontaneous uterine contractions duration only at 0-10 min period, but - did not modify amplitude. This increase in the duration was blocked by naloxone 5 mg ks -1, which had no effect on the amplitude or duration of contractions when given alone. Oxytocin (~T), I, 10 and I 100 mIU (i.v.) stimulated in a dose dependent manner, spontaneous uterine contractions duration but did not alter the amplitude of contractions. Blocking the opioid peptides by naloxone, 5 mg kg -1 (s.c.) injected --10min before OT strongly potentiated the effect of the lowest dose of OT (1 mlU) b-yabout of 59&Ofn and doubled the amplitude of contractions during the 30 min observation period. When acetorphan, 10 mg kg _-1 (i.v.) administered 30 min before the lowest dose of OT studied, 1 mID (i.v.), It induced a slight increase by .about 88% in uterine contractions duration produced by OT alone, The amplitude remained unchanged. These -results suggested that uterine contractions induced by OT in late pregnancy in rats might be regulated by enkephalinergie and enkephalinasic systems

The effects of two enkephalinase inhibitors, acetorphan and thiorphan, and the enkephalin analogue [d-Ala²\p=n-\Met⁵]-enkephalinamide (DAMEA), on spontaneous uterine contractions were studied at day 21 of pregnancy in rats following treatment in vivo or in vitro. Acetorphan (10 mg kg\m=-\1)and thiorphan (1 mg kg\m=-\1),immediately after their i.v. administration, increased the duration of spontaneous contractions 3.4- and 4.6-fold, respectively, but did not modify the maximum amplitude. Similarly, thiorphan (40 \g=m\moll\m=-\1) increased the duration of contractions when administered in vitro. Thiorphan was ineffective during the first 30 min when given into the cerebral ventricles (50 \g=m\gper rat). These results suggest that the enkephalinase inhibitors are acting via a peripheral opioid pathway; and this conclusion is supported by the observation that thiorphan potentiated the stimulatory effect of a submaximal dose of DAMEA administered in vitro. The excitatory effects of DAMEA and the enkephalinase inhibitors were blocked by naloxone. This antagonistic effect of naloxone on uterine motility in the periparturient rat uterus, induced by either acetorphan and thiorphan or DAMEA, seems to be regulated by peripheral opiate receptors. Naloxone (10 mg kg\m=-\1 s.c.) increased both the amplitude and duration of uterine motility in vivo; however, naloxone (26 \g=m\moll\m=-\1 and 52 \g=m\moll\m=-\1) produced a paradoxical dose-dependent biphasic effect in vitro.

The effects of bilateral ovariectomy on uterine motility and levels of progesterone, oestradiol, cAMP, adrenaline and PGF2 alpha were studied in the rat at midpregnancy. Animals were randomly divided into two groups, at least 15 rats in each, sham-operated serving as controls and ovariectomized. The spontaneous uterine mechanical activity of Wistar rats was recorded isometrically and the electrical activities were recorded simultaneously by two bipolar electrodes. Within 30 minutes of ovariectomy a significant increase of the amplitude of uterine contractions was observed and the simultaneity of electrical activity was significantly improved; these effects became more pronounced at 1h post-ovariectomy (p less than 0.005). Plasma progesterone levels decreased by 20% (p less than 0.01) at 30 min and by 50% (p less than 0.001) 1h after ovariectomy, whereas oestrogen levels remained unchanged. Levels of adrenaline, cAMP and PGF2 alpha in the uterine tissue 1h following ovariectomy were affected as follows: adrenaline (p less than 0.05) and cAMP (p less than 0.001) were reduced and PGF2 alpha augmented (p less than 0.05). It appears that variation of the ratio oestrogens/progesterone induces precociously the activation of uterine mobility and exerts an effect on some factors involved in the regulation of the rat myometrium at midpregnancy.