Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 In the rat isolated uterus maximal spontaneous contractions and maximal sensitivity to angiotensin II, oxytocin and prostaglandin F(2alpha) were observed in di- and proestrus. Minimal sensitivity to the three agonists was observed in metoestrus. Maximal contractile effects of angiotensin II, oxytocin and prostaglandin F(2alpha) were thus observed when the ratio oestrogen/progesterone levels was high.2 The oestrogen-dependent sensitivity of the rat uterus is partially mediated by endogenous prostaglandins. Indomethacin suppressed the increased sensitivity to angiotensin and oxytocin present in dioestrus and proestrus but did not affect that to prostaglandin F(2alpha). Polyphloretin phosphate at a concentration of 10 mug/ml resulted in complete identity of dioestrus and metoestrus dose-response curves to angiotensin and oxytocin.3 Spontaneous uterine contractions observed when oestrogen levels are high are also dependent on intramural prostaglandins as they were inhibited by indomethacin and polyphloretin phosphate. In the metoestrus uterus, prostaglandin F(2alpha) induced the reappearance of spontaneous contractions.4 Prostaglandin F(2alpha) had a potentiating effect on angiotensin-elicited contractions which persisted after washing out prostaglandin F(2alpha).
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PMID:Effects of prostaglandin inhibitors on angiotensin, oxytocin and prostaglandin F2 alpha contractile effects on the rat uterus during the oestrous cycle. 437 38

1. Indomethacin and meclofenamate, both of which are potent inhibitors of prostaglandin synthetase, antagonized the contractor effects of oxytocin on the isolated uterus from the non-pregnant rat. Contractions induced by acetylcholine or prostaglandin F(2a) were not antagonized.2. Uteri from rats 17-22 days pregnant exhibited intermittent spontaneous contractions when used as isolated preparations. They also released prostaglandin-like activity (mainly similar to F(2a)) into the bathing fluid. Both the prostaglandin release and the uterine activity were abolished by indomethacin. Activity could be restored by addition of low concentrations of prostaglandin E(2) or F(2a).3. The release of prostaglandin F(2a)-like activity by the uteri increased dramatically on the expected day of delivery (day 22).4. The results add force to the hypothesis that the spontaneous activity of some isolated organs is due to an intramural prostaglandin generation, and that increased uterine prostaglandin production contributes to the expulsion of the foetus.
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PMID:The contribution of prostaglandin production to contractions of the isolated uterus of the rat. 478 6

Prolactin production by human decidua was examined with the use of a short-term tissue explant system. Decidua obtained after normal spontaneous vaginal deliveries produced significantly more prolactin than did tissue obtained after elective repeat cesarean section deliveries in the absence of labor (P less than 0.005). Cytosolic prolactin levels did not differ between the two delivery modes. Oxytocin (4.3 X 10(-11) M to 4.3 X 10(-6) M) and eicosatetraenoic acid (10(-7) M to 10(-4) M) had no effect on prolactin production or storage by decidual tissue. Indomethacin at 10(-4) M reduced only levels of stored prolactin but had no effect on stored or produced prolactin at lower concentrations (10(-7) M to 10(-5) M). Arachidonic acid (10(-4) M) suppressed both production and storage of prolactin (P less than 0.05). Decidual tissue from the two delivery modes did not differ in response to the above agents. Although the exact mechanism(s) remains obscure, these results indicate decidual prolactin production is altered by some aspect of labor. The possible involvement of prostaglandin precursors in mediating this production cannot be excluded.
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PMID:Prolactin secretion by human chorion-decidua in vitro: influences of mode of delivery and agents that modify prostaglandin synthesis. 661 83

1 Eicosatetraynoic acid, the acetylene analogue of arachidonic acid, which inhibits both the cyclo-oxygenase and lipoxygenase pathways, reduced the contractile response of rat uterine smooth muscle to either angiotensin II or oxytocin. 2 Indomethacin, an inhibitor of cyclo-oxygenase, did not reduce the response to angiotensin II but did abolish the contractile response to low doses of oxytocin. 3 Nordihydroguaiaretic acid, a lipoxygenase inhibitor, totally abolished the uterine response to either oxytocin or angiotensin II. 4 The contractile response to carbachol, a cholinoceptor agonist, was unaffected by pretreatment with any of the cyclo-oxygenase or lipoxygenase inhibitors. 5 From these findings, it can be implied that some product of the arachidonate lipoxygenase pathway augments peptide-induced contractions of the rat uterus.
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PMID:Prostaglandin synthesis inhibitors: effect on angiotensin II- and oxytocin-induced contractions in rat uterine smooth muscle. 687 37

Both oxytocin (OT) and prostaglandin (PG) possess potent uterotonic activity. It has been suggested that the uterotonic action of OT may be mediated by PG release. We investigated the uterotonic and PG-releasing actions of OT, angiotensin II (AT) and methacholine (MC) in isolated pregnant rat uteri. Our findings indicate that the OT-induced PG release is a direct effect of OT and not a secondary response to myometrial contractions and that the uterotonic action of OT is not dependent on PG participation. This is shown by: 1) equipotent uterotonic doses of OT, AT and MC had different effects on uterine PG release. OT and AT caused uterine contractions and PG release, whereas MC caused contractions but no PG release. 2) OT produced a dose-dependent uterotonic responses. However, there was no proportional relationship and the rate of PG release. 3) In uterine homogenates, which lack the functional integrity for mechanical contractions, OT also caused an increase in PG biosynthesis. Indomethacin suppressed both the spontaneous and the OT-stimulated PG synthesis in the uterine homogenates. 4) In isolated uterine horns, the contractile response to OT was only slightly attenuated in the presence of indomethacin sufficient to inhibit completely the OT-stimulated PG synthesis. We concluded that OT has a dual action in the uterus and may act on two different receptors, one leading to myometrial contractions and the other leading to PG release. AT, an octapeptide like OT, may also have a dual action, whereas the parasympathomimetic, MC, has predominately a direct uterotonic action.
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PMID:The separate uterotonic and prostaglandin-releasing actions of oxytocin. Evidence and comparison with angiotensin and methacholine in the isolated rat uterus. 720 17

The effect of angiotensin II and [Sar1,Ile5,Ala8]-angiotensin II on uterine contractions and the relationship of uterine prostaglandins to these effects were studied. Uterine segments from pregnant rats were monitored in vitro for isometric contractile activity in Krebs-Ringer medium (95% O2-5% CO2; 37 C). The medium was sampled periodically and assayed for prostaglandin E2, prostaglandin F2 alpha, and 13,14-dihydro-15-keto-prostaglandin F2 alpha by RIA. Angiotensin II increased frequency of contractions and integrated contractile force in a dose-related fashion. Angiotensin II (1 microgram) resulted in increased prostaglandin (PG) production, but there was no clear dose-related effect. Indomethacin significantly reduced PG production (P < 0.001); however, the contractile response to angiotensin II was not affected. [Sar1,Ile5,Ala8]Angiotensin II had no effect on spontaneous contractile activity or PG production in uteri from 18 or 21 days of pregnancy, nor did [Sar1,Ile5,Ala8]angiotensin II affect oxytocin-stimulated uterine contractions. [Sar1,Ile5,Ala8]Angiotensin II (2.5 microgram) did inhibit (P < 0.05) uterine contractions induced by angiotensin II (0.5 microgram), but PG production was not affected. In conclusion, the studies described provide evidence that angiotensin II-induced uterine contractions of in vitro pregnant rat uteri are not dependent upon increased PG production.
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PMID:Angiotensin II and [Sar1, Ile5, Ala8]angiotensin II effect on contractile activity and prostaglandin production of in vitro pregnant rat uteri. 742 93

The oxytocic activity of the hot methanol extract (HME) of the leaves of Monechma ciliatum was compared with other uterine stimulants like ergometrine, oxytocin, 5-hydroxytryptamine (5-HT), acetylcholine (ACh) and prostaglandins (PGs) E2 and F2alpha (PGE2 and PGF2alpha) in the presence of some antagonists in an attempt to explain the mechanism of action of the extract. The effects of the reference drugs on uteri isolated from rats pretreated with HME for 2 weeks were also observed. Atropine blocked the effect of ACh and partially blocked those of HME while L-366-948 blocked only the effect of oxytocin. Indomethacin inhibited the effects of HME as well as all the other drugs, except the PGs and ACh. D-600 blocked the effect of all the drugs including HME. Methysergide antagonised only the effect of 5-HT and partially blocked ergometrine. Prolonged treatment altered the uterine musculature and the activity profile of the reference drugs. These results suggest that the HME may be acting by more than one mechanism to contract the uterus and explains the mechanism of the anti-implantation activity of the plant.
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PMID:Uterotonic properties of the methanol extract of Monechma ciliatum. 984 29

Prematurity is the leading cause of neonatal morbidity and mortality, yet the incidence of preterm birth has not declined despite the use of multiple pharmacological agents to treat preterm labour. After reviewing the literature we conclude the following. beta-Agonists have been shown to prolong gestation for 24 to 48 hours; however, these agents have not been shown to decrease neonatal morbidity or mortality. Adverse effects are inevitable and can be life-threatening. There are no proven benefits to mother or fetus with long term therapy. More data are needed regarding the tolerability and efficacy of calcium antagonists before routine clinical use can be recommended. Oxytocin antagonists should be considered investigational drugs and further studies are needed to evaluate their effectiveness in the treatment of preterm labour. Furthermore, the tolerability of oxytocin antagonists in both mother and fetus has not been adequately established. Indomethacin, a prostaglandin inhibitor, has been shown to delay delivery in a limited number of randomised placebo-controlled clinical trials. Sulindac appears promising but has never been evaluated in a well controlled trial. Neonatal adverse effects appear to be minimal with prostaglandin inhibitors as long as the duration of treatment is short (<48 to 72 hours) and the gestational age is <32 weeks. Magnesium sulfate appears to inhibit myometrial contractility but is ineffective at prolonging gestation or preventing preterm birth. Furthermore, magnesium has not been shown to decrease neonatal morbidity or mortality; in fact, some investigators have shown an increase in infant mortality with this agent. There are no data to support adjunctive antimicrobial therapy for the treatment of preterm labour. Oral maintenance therapy with any of these tocolytic agents has not been shown to decrease the rate of preterm birth or recurrent preterm labour.
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PMID:A risk-benefit assessment of therapies for premature labour. 1043 52

Decoctions of Agapanthus africanus and Clivia miniata are used as oxytocic agents in South African traditional herbal medicine. Aqueous extracts of A. africanus and C. miniata leaves have been shown to possess similar uterotonic activities in the isolated whole uterus preparation. The uterus however, comprises a myometrial and an endometrial layer and the activity of both oxytocin and the prostaglandins differs in these layers. The aim of this study was to determine the uterotonic activity of the herbal remedies in an endometrium-free preparation (i.e. "stripped" myometrium) and, if active, whether this effect could be related to prostaglandin synthesis or to interaction with specific receptors. The effects of the herbal extracts were tested on the isolated "stripped" rat myometrium preparation. Both herbal extracts caused a direct contractile response by the isolated tissue. Pretreatment of the myometrium with either plant extract augmented the initial response to acetylcholine. Preincubation with atropine inhibited the response to cumulative dosage of Agapanthus extract but had no effect on the response to Clivia. Indomethacin administration did not affect the response of the myometrium to cumulative dosage of acetylcholine, oxytocin or Clivia extract but inhibited the response to Agapanthus extract. These results clearly indicate that the Agapanthus and Clivia herbal extracts exhibited uterotonic activity in this model. The study illustrates that the "stripped" myometrium model has successfully differentiated between the mechanisms of action of two herbal oxytocics compared to the whole uterus preparation where their uterotonic activity was thought to be similar.
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PMID:The effects of herbal oxytocics on the isolated "stripped" myometrium model. 1097 6

In the pig, nest building occurs in the day preceding parturition (gestation=114--116 days). Nest building behaviour can be induced in pregnant, pseudopregnant and cyclic female pigs following injection of prostaglandin F2alpha. Here we investigated behaviour and endocrine changes after the administration of indomethacin, which inhibits cyclo-oxygenase enzymes and thus prostaglandin synthesis. In experiment 1, pregnant primiparous pigs (gilts) were blood sampled through jugular vein catheters every 20 min from 1000 h on day 113 of pregnancy and behaviour was recorded until birth. Two hours after pre-partum nest building began, animals received 4 mg/kg indomethacin (n=7) or control vehicle (n=8) intramuscularly. Indomethacin-treated animals showed less nest building than controls between 1 and 5 h after injection (P<0.05), during which time they were mostly inactive and lay down for longer than controls. From 5 h before birth until birth there was no significant treatment difference in nest building behaviour. There was a tendency for the start of birth to be delayed in indomethacin-treated animals. Plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (a major metabolite of prostaglandin F2 alpha) rose during pre-injection nest building and then fell following indomethacin treatment, but was not significantly different between groups when behaviour differed. Plasma oxytocin, cortisol and progesterone were not significantly affected by treatment. In experiment 2, indomethacin-treated non-pregnant gilts (n=7) did not show any changes in activity or posture compared with vehicle-treated controls (n=6) between 90 and 150 min after treatment. These results suggested that indomethacin treatment reversibly and specifically inhibits porcine pre-partum nest building by a mechanism that may involve endogenous prostaglandin F2 alpha synthesis inhibition but is independent of circulating oxytocin, cortisol and progesterone concentrations.
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PMID:Indomethacin blocks pre-partum nest building behaviour in the pig (Sus scrofa): effects on plasma prostaglandin F metabolite, oxytocin, cortisol and progesterone. 1187 99


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