dinoprost and atosiban

To examine the effects of atosiban, given before transfer of frozen-thawed embryo to women with endometriosis (EMs).. A randomized, controlled clinical trial.. University hospital and IVF center.. One hundred twenty women with endometriosis undergoing frozen-thawed embryo transfer were randomly allocated into the atosiban treatment and the control groups. Another 120 women with infertility due to tubal factor were enrolled into a tubal factor group, to compare serum oxytocin (OT) and prostaglandin (PG)F2α levels and uterine contractions with the endometriosis group.. In the endometriosis treatment group, a single bolus (6.75 mg, 0.9 mL per vial) of atosiban was administrated before ET.. Implantation rate and pregnancy rate.. Serum OT level (1.89 ± 0.33 vs. 1.66 ± 0.32 ng/L), PGF2α (2.83 ± 0.34 vs. 2.36 ± 0.35 ng/L) level, and uterine contractions (2.5 ± 1.2 vs. 1.8 ± 1.0 waves per minute) in the endometriosis group were all significantly higher than in the tubal factor group. The clinical pregnancy rate per cycle and implantation rate per transfer were 58.3% and 41.0%, respectively, in the atosiban treatment group, significantly higher than in the control group (38.3% and 23.4%, respectively).. Women with endometriosis showed higher serum OT level, PGF2α level, and uterine contractions. Atosiban treatment before ET in endometriosis is effective in the priming of the uterus, suitable for embryo implantation. This is the first study to evaluate the effect of atosiban treatment in patients with endometriosis.. ChiCTR-IOQ-14005715.

Topics: Adult; Biomarkers; China; Cryopreservation; Dinoprost; Drug Administration Schedule; Embryo Implantation; Embryo Transfer; Endometriosis; Female; Fertility; Fertilization in Vitro; Hormone Antagonists; Hospitals, University; Humans; Infertility, Female; Middle Aged; Oxytocin; Pregnancy; Pregnancy Rate; Prospective Studies; Time Factors; Treatment Outcome; Uterine Contraction; Vasotocin; Young Adult

We compared menstrual pain, uterine contractility and blood circulation, and plasma concentrations of vasopressin and prostaglandin F(2alpha) metabolite in women with versus without primary dysmenorrhea, and determined the effects of a vasopressin antagonist, 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-oxytocin (Atosiban), on these parameters. Our results do not support the contention that vasopressin is involved in the etiology of dysmenorrhea, plasma concentrations of vasopressin being similar in dysmenorrheic women and controls, and the vasopressin antagonist Atosiban having no effect on menstrual pain, intrauterine pressure or uterine artery pulsatility index in dysmenorrheic women.

Topics: Adult; Blood Flow Velocity; Cross-Over Studies; Dinoprost; Double-Blind Method; Dysmenorrhea; Female; Hormone Antagonists; Humans; Uterine Contraction; Uterus; Vasopressins; Vasotocin

What is the in-vitro effect of oxytocin receptor (OTR) antagonism on parameters of receptivity in human endometrial explants and endometrial stromal cell lines cultured in oestradiol-rich conditions mimicking ovarian stimulation?. Experimental in-vitro study on endometrial tissue explants collected by aspiration biopsy from 30 women undergoing fertility treatment and cultured endometrial tHESC cell line. The study examined the effects of high oestradiol, oxytocin and OTR antagonist on parameters of decidualization (cell viability and prolactin secretion) as well as cyclooxygenase-1/2 (COX-1/2) activity and prostaglandin F. In experiments on cultured endometrial cell line, high oestradiol and oxytocin similarly limited the viability of cells. In cultured endometrial explants both also decreased the secretion of prolactin (a marker of decidualization) and augmented endometrial COX-2 activity and formation of PGF. Oxytocin antagonist reversed the effects of high oestradiol and oxytocin on parameters related to endometrial receptivity in conditions mimicking ovarian stimulation. This might point to a novel, endometrium-related mechanism to support embryo implantation achieved by the application of oxytocin antagonist prior to embryo transfer.

Topics: Adult; Biopsy; Cell Line; Cell Survival; Cells, Cultured; Decidua; Dinoprost; Embryo Implantation; Endometrium; Estradiol; Estrogens; Female; Humans; Ovulation Induction; Oxytocin; Prolactin; Prostaglandin-Endoperoxide Synthases; Receptors, Oxytocin; Vasotocin

Topics: Adult; Anti-Inflammatory Agents; Calcium; Cells, Cultured; Cyclooxygenase 2; Dinoprost; Female; Humans; MAP Kinase Signaling System; Muscle Contraction; Myometrium; NF-kappa B; Oximes; Oxytocin; Pregnancy; Pyrrolidines; Tocolytic Agents; Vasotocin

Uterine inflammation results in a poor uterine environment and early embryonic loss in the mare due to an inhibition of maternal recognition of pregnancy caused from increased prostaglandin F2α (PGF2α). Oxytocin binds to endometrial cell receptors to activate prostaglandin synthesis. An oxytocin receptor antagonist (Atosiban) and a cyclooxygenase inhibitor (indomethacin) both decrease PGF2α production. The aim of this study was to evaluate the in vitro effects of Atosiban and indomethacin on equine uterine prostaglandin secretion. Equine endometrial explants were harvested on day two of behavioral estrus. Endometrial explant cultures were challenged with oxytocin (250nM) and PGF2α concentrations were measured over time. Explants were also cultured with Atosiban and indomethacin for 6h to determine the influence on PGF2α secretion. When endometrial explants were challenged with oxytocin, PGF2α concentrations were greater (P<0.0001) at each time point over the 24h of culture as compared to controls. Oxytocin failed (P<0.001) to elicit PGF2α release in explants cultured with either Atosiban or indomethacin. These findings show equine endometrial explants can be stimulated with oxytocin to increase secretion of PGF2α and this secretion can be inhibited through an oxytocin receptor antagonist and a Cox inhibitor, suggesting that this response to oxytocin involves an oxytocin receptor mediated event that activates the prostaglandin synthesis cascade through cyclooxygenase. Furthermore, this data suggests a role for the use of these inhibitors in vivo to decrease uterine PGF2α secretion and prevent early luteal regression and embryonic loss.

Topics: Animals; Biopsy; Cyclooxygenase Inhibitors; Dinoprost; Endometrium; Female; Hormone Antagonists; Horses; Indomethacin; Least-Squares Analysis; Organ Culture Techniques; Oxytocin; Receptors, Oxytocin; Vasotocin

The release of arachidonic acid from membrane glycerophospholipids through the action of phospholipases (PLs) is the first step in the biosynthesis of prostaglandins (PGs). In reproductive tissues, the most important PLs are cytosolic PLA(2) (cPLA(2)) and types IIA and V of the secretory isoform (sPLA(2)). The aim of this work was to investigate the role of ovarian steroid hormones and oxytocin (OT) in the regulation of rat uterine PLA(2) activity and expression during pregnancy and labor. The activity of sPLA(2) increased near labor, whereas cPLA(2) activity augmented towards the end of gestation. The levels of sPLA(2) IIA and cPLA(2) mRNA showed an increase before labor (P<0.05, day 21), whereas sPLA(2) V mRNA was not regulated during pregnancy. The administration of atosiban (synthetic OT antagonist) together with tamoxifen (antagonist of estrogen receptors) was able to decrease cytosolic and secretory PLA(2) activities, diminish the expression of sPLA(2) IIA and cPLA(2), as well as decrease PGF(2 alpha) production before the onset of labor (P<0.01). The ovarian steroid did not affect PLA(2) during pregnancy. Collectively, these findings indicate that in the rat uterus, both 17beta-estradiol and OT could be regulating the activity and the expression of the secretory and the cytosolic isoforms of PLA(2), thus controlling PGF(2 alpha) synthesis prior to the onset of labor.

Topics: Animals; Cytosol; Dinoprost; Estradiol; Estrogen Antagonists; Female; Gene Expression; Isoenzymes; Labor, Obstetric; Mifepristone; Oxytocin; Phospholipases A2; Pregnancy; Progesterone; Rats; Rats, Wistar; Receptors, Oxytocin; Reverse Transcriptase Polymerase Chain Reaction; Tamoxifen; Uterus; Vasotocin

The present study examined the role of intra-luteal prostaglandin (PG) F(2alpha), progesterone (P4) and oxytocin (OT) on the corpus luteum function by using specific hormone antagonists. Luteal cells from the developing CL (days 5-7 of the estrous cycle) were exposed to P4 antagonist (onapristone, OP, 10(-4)M), OT antagonist (atosiban, AT; 10(-6)M) or indomethacin (INDO; 10(-4)M), for 12h and then stimulated with PGF(2alpha) (10(-8)M) for 4h. Pre-treatment of the cells with OP, AT or INDO resulted in an increase in P4 secretion in response to PGF(2alpha). To examine the temporal effects of P4, OT and PGs on P4 secretion, dispersed luteal cells were pre-exposed to OP, AT or INDO for 1, 2, 4, 6 or 12h. Prostaglandin F(2alpha) stimulated P4 secretion (P<0.05) after 2h of pre-exposition. In the microdyalisis study, the spontaneous release of P4 from developing CL tissue was of pulsatile nature with irregular peaks at 1-2h intervals. Treatment with OP increased the number of P4 peaks (P<0.05), whereas AT and INDO significantly reduced the number of P4 peaks detected (P<0.05). Interestingly, INDO completely blocked the pulsatile nature in the release of P4, but it secretion remained stable throughout the experimental period. These results demonstrate that luteal PGF(2alpha), OT, and P4 are components of an autocrine/paracrine intra-ovarian regulatory system responsible for the episodic (pulsatile) release of P4 from the bovine CL during the early luteal phase.

Topics: Animals; Cattle; Cells, Cultured; Corpus Luteum; Dinoprost; Dose-Response Relationship, Drug; Female; Hormone Antagonists; Indomethacin; Luteal Phase; Oxytocin; Progesterone; Time Factors; Vasotocin

The aim of this study was to compare the effects of the selective prostaglandin synthase type 2 inhibitor nimesulide, alone or in combination with the oxytocin receptor antagonist atosiban, on the progression of glucocorticoid-induced premature labor in sheep. Effects on circulating maternal and fetal prostaglandin concentrations and on fetal well-being were also examined.. Premature labor was induced in ewes with long-term catheterized fetuses by infusion of dexamethasone (1 mg/d) starting at 138 +/- 1 days' gestation. Ewes also received an infusion of either nimesulide and atosiban (20.0 and 4.12 mg/kg per day, respectively; n = 5), nimesulide alone (20.0 mg/kg per day; n = 5), or vehicle only (n = 9). Plasma 13,14-dihydro-15-keto-prostaglandin F(2)(alpha) and prostaglandin E(2) concentrations were measured before and during infusions in plasma samples obtained from the maternal and fetal carotid arteries and the utero-ovarian vein.. No fetuses from ewes treated with nimesulide and atosiban were delivered during treatment. These animals were killed electively 98.0 +/- 6.8 hours after the commencement of dexamethasone induction. This was significantly longer than the delivery times for those ewes treated with nimesulide alone (71.2 +/- 3.9 hours; n = 5) and for vehicle-treated ewes (51.4 +/- 1.7 hours; n = 9). Both maternal and fetal plasma 13, 14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations in nimesulide and atosiban-treated ewes and in nimesulide-treated ewes decreased during treatment. In contrast, vehicle-treated ewes showed a significant increase in maternal and fetal plasma 13,14-dihydro-15-keto-prostaglandin F(2alpha) and prostaglandin E(2) concentrations during dexamethasone induction. Uterine electromyographic activity observed in nimesulide and atosiban-treated ewes was significantly suppressed with respect to activities in both vehicle- and nimesulide-treated ewes during the treatment period. All fetuses were alive at delivery or scheduled death.. These results indicate that the combination of an inhibitor of prostaglandin endoperoxidase H synthase type 2 with an oxytocin receptor antagonist is more effective in inhibition of preterm labor than is treatment with a prostaglandin endoperoxidase H synthase type 2 inhibitor alone. The clinical use of atosiban to prevent the oxytocin-stimulated increase in uterine activity associated with labor in combination with nimesulide may permit reduction of the dose of nimesulide used to a level that has minimal impact on fetal well-being.

Topics: Animals; Arteries; Blood Glucose; Cyclooxygenase Inhibitors; Dexamethasone; Dinoprost; Dinoprostone; Drug Therapy, Combination; Electromyography; Female; Fetal Blood; Fetus; Glucocorticoids; Lactic Acid; Obstetric Labor, Premature; Oxygen; Pregnancy; Receptors, Oxytocin; Sheep; Sulfonamides; Uterus; Vasotocin

In the present study we have shown that the genetic expression of prostaglandin (PG)F(2alpha) receptor (R) and cyclooxygenase (COX)-2 increases in laboring rat myometrium. This finding was associated with a relatively weak contractile in vitro response (E:(max)) of isolated uterine strips when challenged with PGF(2alpha). Five days postpartum PGF(2alpha)-R mRNA values exceeded those during labor while COX-2 mRNA was reduced to preparturient values. Maximal contractility of isolated strips stimulated with PGF(2alpha) at this time was enhanced and E:C(50) decreased. Oxytocin treatment of estrogen-primed nonpregnant rats down-regulated uterine contractile responsiveness to PGF(2alpha), leaving mRNA values for this receptor unchanged, whereas oxytocin receptor blockade with atosiban (an oxytocin receptor antagonist) left E:(max) unaltered. In contrast, atosiban treatment of pregnant rats resulted in a 2.5-fold increase in E:(max) and a considerably reduced EC(50) during labor when compared to untreated delivering rats. The increased contractile ability was associated with a threefold increase in PGF(2alpha)-R mRNA production, indicating that the regulation by atosiban of the PGF(2alpha)-induced response is exerted at the genetic level. Based on the present data we suggest that 1) PGF(2alpha)-R stimulation may not primarily exert a contracting role in the normally delivering myometrium, and 2) the presence of the PGF(2alpha)-R system in rat myometrium may explain the apparent functional redundancy of the oxytocinergic system during the process of birth in animals lacking oxytocin or where the oxytocin receptor is blocked. In this context PGF(2alpha) receptor stimulation may, in the absence of oxytocin receptor stimulation, exert the contractile forces needed for proper propulsion of the fetus.

Topics: Animals; Cyclooxygenase 2; Dinoprost; Female; In Vitro Techniques; Isoenzymes; Myometrium; Oxytocics; Prostaglandin-Endoperoxide Synthases; Rats; Receptors, Oxytocin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tocolytic Agents; Uterine Contraction; Vasotocin

Subluteolytic doses of prostaglandin F2alpha analogue (oestrophan) given i.m. and oxytocin (OT) antagonist (CAP) and noradrenaline (NA) infused into the abdominal aorta were used to test the importance of luteal OT in pulsatile secretion of prostaglandin F2alpha (PGF) during luteolysis in heifers (n = 17). In experiment 1, heifers were pre-infused for 30 minutes with saline on either day 17 of the oestrous cycle (group 1; n = 4) or on day 18 of the oestrous cycle (group 2; n = 3), and with CAP (8 mg per animal) on day 17 of the oestrous cycle (group 3; n = 4). Next, heifers were injected with oestrophan (30 microg per animal). Injection of oestrophan in Group 3 increased OT concentrations (P < 0.001) to values similar to those observed during spontaneous luteolysis (50 to 70 pg ml(-1)). PGFM concentrations in this group also increased (P < 0.001), but were lower (P < 0.05) than the values in groups 1 and 2, CAP given prior to oestrophan decreased both PGFM elevation (P < 0.06) and its area under the curve (P < 0.01), compared to the saline pretreated heifers. In experiment 2 NA (4 mg) was infused twice for 30 minutes at five hour intervals to release OT on day 17 of the oestrous cycle (n = 6). However, during hormone analysis it appeared that three of six heifers had elevated PGFM concentrations (group 1) and three others did not (group 2). NA caused the correlated increase of progesterone and OT secretion (r = 0.68; P < 0.05) in both groups but it only influenced PGF secretion in group 1 only (P < 0.05). We postulate that OT can amplify and modulate the course of induced luteolysis as a regulator of the amplitude of pulsatile PGF secretion. PGF analogue stimulates secretion of endogenous PGF from the uterus in cattle and this may be an important component of the luteolytic response to exogenous PGF.

Topics: Animals; Aorta, Abdominal; Cattle; Cloprostenol; Dinoprost; Estrus; Female; Hormone Antagonists; Infusions, Intravenous; Injections, Intramuscular; Norepinephrine; Oxytocin; Progesterone; Vasotocin

Prostaglandin (PG) F2alpha that is released from the uterus is essential for spontaneous luteolysis in cattle. Although PGF2alpha and its analogues are extensively used to synchronize the estrous cycle by inducing luteolysis, corpora lutea (CL) at the early stage of the estrous cycle are resistant to the luteolytic effect of PGF2alpha. We examined the sensitivity of bovine CL to PGF2alpha treatment in vitro and determined whether the changes in the response of CL to PGF2alpha are dependent on progesterone (P4), oxytocin (OT), and PGs produced locally. Bovine luteal cells from early (Days 4-5 of the estrous cycle) and mid-cycle CL (Days 8-12 of the estrous cycle) were preexposed for 12 h to a P4 antagonist (onapristone: OP; 10(-4) M), an OT antagonist (atosiban: AT; 10(-6) M), or indomethacin (INDO; 10(-4) M) before stimulation with PGF2alpha. Although OP reduced P4 secretion (p < 0.001) only in early CL, it reduced OT secretion in the cells of both phases examined (p < 0.001). OP also reduced PGF2alpha and PGE2 secretion (p < 0.01) from early CL. However, it stimulated PGF2alpha secretion in mid-cycle luteal cells (p < 0.001). AT reduced P4 secretion in early and mid-cycle CL (p < 0.05). Moreover, PGF2alpha secretion was inhibited (p < 0.05) by AT in early CL. The OT secretion and the intracellular level of free Ca2+ ([Ca2+]i) were measured as indicators of CL sensitivity to PGF2alpha. PGF2alpha had no influence on OT secretion, although [Ca2+]i increased (p < 0.05) in the early CL. However, the effect of PGF2alpha was augmented (p < 0.01) in cells after pretreatment with OP, AT, and INDO in comparison with the controls. In mid-cycle luteal cells, PGF2alpha induced 2-fold increases in OT secretion and [Ca2+]i. However, in contrast to results in early CL, these increases were magnified only by preexposure of the cells to AT (p < 0.05). These results indicate that luteal P4, OT, and PGs are components of an autocrine/paracrine positive feedback cascade in bovine early to mid-cycle CL and may be responsible for the resistance of the early bovine CL to the exogenous PGF2alpha action.

Topics: Animals; Calcium; Cattle; Cells, Cultured; Corpus Luteum; Dinoprost; Dinoprostone; Estrus; Female; Gonanes; Hormone Antagonists; Indomethacin; Oxytocin; Progesterone; Prostaglandin Antagonists; Prostaglandins; Vasotocin

The role of oxytocin (OT) in the regulation of prostaglandin F2 alpha (PGF2 alpha) secretion during luteolysis in gilts was studied using a highly specific OT antagonist (CAP-581). In Experiment 1 gilts on Days 14 to 19 of the oestrous cycle in Latin square design were used, to determine the dose and time of application of OT and CAP. In Group I (n = 6) gilts were treated intravenously with saline or with 10, 20 and 30 IU of OT. Concentrations of the main PGF2 alpha metabolite i.e. 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in blood samples as uterine response to the treatment. Twenty IU of OT was the most effective to stimulate PGFM release and this dose was used after CAP treatment in gilts of Groups II, III and IV. Gilts of Group II (n = 3) were injected into the uterine horns (UH) with saline (5 ml/horn) or CAP (2 mg, 3 mg and 4 mg; half dose/horn) and OT was injected (i.v.) 30 min thereafter. Any of the CAP doses given into the UH affected PGFM plasma concentrations stimulated by OT. In Group III (n = 4) gilts were infused (i.v.) for 30 min with CAP (9 mg, 14 mg and 18 mg/gilt) followed by 20 IU of OT. All doses of CAP effectively inhibited OT-stimulated PGF2 alpha release, therefore 9 mg was selected for the further studies. Gilts of Group IV (n = 4) received OT 4, 6 and 8 h after CAP to define how long CAP blocks the OT receptors. Concentrations of PGFM increased after any of this period of time. Thus, we concluded that 9 mg of CAP infused every 4 h will effectively block OT receptors. In Experiment 2, gilts (n = 4) received CAP as a 30-min infusion every 4 h on Days 12-20 of the oestrous cycle. Control gilts (n = 3) were infused with saline. CAP infusions diminished the height of PGFM peaks (P < 0.05). Frequency of the PGFM (P < 0.057) and OT (P < 0.082) peaks only tended to be lower in the CAP-treated gilts. Peripheral plasma concentrations of progesterone (P4) and oestradiol-17 beta (E2) and the time of luteolysis initiation as measured by the decrease of P4 concentration were the same in CAP- and saline-treated gilts. The macroscopic studies of the ovaries in gilts revealed lack of differences between groups. We conclude that OT is involved in the secretion of luteolytic PGF2 alpha peaks but its role is limited to controlling their height and frequency. Blocking of OT receptors did not prevent luteolysis in sows.

Topics: Animals; Corpus Luteum; Dinoprost; Estradiol; Estrus; Female; Hormone Antagonists; Oxytocin; Progesterone; Radioimmunoassay; Swine; Vasotocin

The oxytocin receptor antagonist [1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Om]-oxytocin (Atosiban) is a specific antagonist of both mesotocin- and oxytocin-induced myometrial contractions in late pregnant tammars in vitro. Continuous intravenous infusion of Atosiban (1 mg kg-1 day-1) for 3 or 7 days from day 24 of the 26.5 day gestation significantly delayed births. In both the 3 day and 7 day infusion groups, all 15 control animals were pregnant and gave birth within the normal time (day 26.75 +/- 0.20, mean +/- SEM), during the infusion of saline. The neonates weighed 387 +/- 8 mg. Deliveries were observed in 15 Atosiban-treated animals significantly (P < 0.05) later than in the controls (day 27.85 +/- 0.19; neonate weight 413 +/- 9 mg). All pouch young were successfully suckled, even in the continued presence of Atosiban. Baseline plasma concentrations of the prostaglandin F metabolite (PGFM) in pregnant tammars were < 200 pg ml-1. A surge in plasma PGFM occurred at birth (811 +/- 116 pg ml-1), followed by a rapid fall to baseline concentrations within 1 h after birth. This was observed both in saline- and in Atosiban-treated animals that gave birth during the observation period, and did not differ significantly between the treatment groups. Plasma progesterone concentrations in the control and the Atosiban-treated animals showed the normal pattern of luteolysis immediately after birth. Thus, infusion of an oxytocin receptor antagonist at the end of gestation delays birth, the peripartum surge in prostaglandin release, and the fall in progesterone, suggesting that mesotocin is an important part of the hormonal cascade associated with delivery in this marsupial.

Topics: Animals; Dinoprost; Female; In Vitro Techniques; Labor, Obstetric; Macropodidae; Myometrium; Oxytocin; Pregnancy; Progesterone; Receptors, Oxytocin; Tocolytic Agents; Vasotocin

The oxytocin receptor inhibitor 1-deamino-2-D-Tyr-(oET)-4-Thr-8-orn-oxytocin (CAP) was infused into late pregnant sheep. Basal and oxytocin-induced prostaglandin (PG) concentrations in maternal and fetal plasma were determined. CAP had no significant effect on maternal PGFM or PGE2 or fetal PGF2 alpha, PGFM or PGE2 concentrations during late pregnancy or at term. PGF2 alpha was not detectable in maternal peripheral plasma. CAP infusion did not affect fetal well-being. Oxytocin injection to the mother caused a significant, dose-dependent, increase in maternal plasma PGFM concentrations but did not alter maternal PGE2 concentrations or fetal PGF2 alpha and PGE2 concentrations. The increase in maternal PGFM concentrations brought about by oxytocin injection was decreased during intrauterine infusion of CAP over the range of 12.5-100 micrograms/min. A rationale for the use of oxytocin receptor blockade for the prevention of premature labor is thus provided.

Topics: Animals; Dinoprost; Dinoprostone; Female; Fetal Blood; Oxytocin; Pregnancy; Pregnancy, Animal; Prostaglandins; Receptors, Oxytocin; Sheep; Vasotocin

Binding of [3H]oxytocin to isolated myometrial plasma membranes was not affected by the presence of prostaglandin (PG)F2 alpha or E2 in the incubation medium. Long-term treatment with PGF2 alpha or indomethacin had no effect on oxytocin receptor concentrations and dissociation constants of myometrial plasma membranes nor on maximal contractility or KM values of isolated uterine strips exposed to oxytocin. Infusion of oxytocin for 5 days in non-pregnant rats resulted in a decrease in oxytocin receptor concentrations in myometrial plasma membranes whereas the binding affinity to oxytocin was unaffected. Isolated uterine strips from similarly treated rats showed a reduced maximal contractile response to oxytocin and an elevated KM value, possibly indicating an influence of oxytocin on the coupling between receptor occupancy and contractility. Treatment for 5 days with desamino1-[D-Tyr(O-ethyl)2-Thr4-Orn8] oxytocin (an oxytocin antagonist) increased the concentration of myometrial oxytocin receptors. In addition KD values of these receptors were elevated. The present results indicate that prolonged exposure to oxytocin leads to a down-regulation of the myometrial receptor concentration, which is not caused by ligand-receptor interaction in itself. The concerted effect of oxytocin and prostaglandins on myometrial contraction does not appear to involve modulation of the oxytocin receptor by prostaglandins.

Topics: Animals; Cell Membrane; Dinoprost; Estradiol; Female; In Vitro Techniques; Indomethacin; Kinetics; Myometrium; Oxytocin; Prostaglandins F; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Oxytocin; Uterine Contraction; Vasotocin