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)

Gemeprost (16,16-dimethyl-trans-delta2 Prostaglandin E1-methyl ester) is a synthetic analogue of Prostaglandin E. It is used to induce midtrimester abortion. 40 women, with diagnoses of fetal abnormality or fetal death in utero, were given a 1 mg Gemeprost pessary in the posterior vaginal fornix. After resting for 30 minutes, the patients were free to move around. The treatment was repeated every 3 hours, until either the products of conception were expelled or 5 pessaries had been inserted. If delivery did not occur within 12 hours, oxytocin infusion was commenced. 42% of the patients delivered with Gemeprost alone, and only 17.5% required surgery. Side effects were few and included incomplete abortion, fever, vomiting, diarrhea, and bleeding. Gemeprost is considered safer and simpler than its alternative, extraamniotic infusion of Prostaglandin F2 alpha.
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PMID:Vaginally administered 16,16-dimethyl-PGE1-methyl ester (Gemeprost) to induce termination of pregnancy after the first trimester. 323 78

Arginine vasopressin (AVP) is thought to act as an antipyretic in the ventral-septal area (VSA) of the brain. As AVP content of this area has been shown to be virtually eliminated following long-term castration, we have tested the hypothesis that castrated rats would display enhanced fevers. Four months after castration (or sham castration), male Wistar rats were given prostaglandin E1 (200 ng), purified interleukin 1 (25 U), or saline (5 microliters) into a lateral cerebral ventricle. Castrated rats displayed fevers of longer duration, reflected as significantly enhanced thermal indexes, than did age-matched sham-operated controls. Castrated rats also were less able to defend their body temperatures to ambient heat stress but not to ambient cold. AVP content of VSA and lateral septum, but not of hippocampus, of castrated rats was significantly reduced; oxytocin content of the three areas was unchanged following castration. These data support earlier studies concerning effects of castration on septal AVP content and are consistent with the possibility that AVP is an antipyretic in the VSA of the rat.
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PMID:Enhanced fever following castration: possible involvement of brain arginine vasopressin. 325 31

To observe the changes in endogenous oxytocics during spontaneous and induced labor, the plasma concentrations of oxytocin, prostaglandin E1 (PGE1) and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured during labor in 9 cases of spontaneous labor (group 1), 10 of PGE2-induced labor (group 2), and 7 of PGF2 alpha-induced labor (group 3). Unextracted samples were used for radioimmunoassay of oxytocin. PGE and PGF were extracted and separated for radioimmunoassays of PGE1 and PGFM. Although oxytocin levels in groups 1 and 3 did not change during labor or slightly increased toward delivery, those in group 2 decreased as labor progressed. The mean oxytocin in group 2 was significantly lower at the times of established labor (15.3 +/- 3.2 microU/ml, mean +/- SE) and crowing of the fetal head (10.8 +/- 2.0 microU/ml) than before labor (52.7 +/- 14.8 microU/ml). Plasma PGE1 levels in groups 1 and 3 were low and did not change during labor. Plasma PGFM levels in groups 1 and 2 gradually rose toward delivery. These results suggest that exogenous PGE2 suppresses oxytocin secretion during labor and stimulates endogenous PGF2 alpha production, that endogenous PGE1 may not play an important role in the progress of spontaneous and PGF2 alpha-induced labor, and that endogenous PGF2 alpha may participate in the promotion of all kinds of labor.
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PMID:Changes in plasma oxytocin, prostaglandin E1, and 13,14-dihydro-15-keto-prostaglandin F2 alpha during labor induced by prostaglandin E2 or F2 alpha and spontaneous labor. 347 3

The effects of prostacyclin (PGI2) on the uterine muscle of pregnant rats were studied in terms of uterine contraction and the variation in cyclic nucleotides. The following results were obtained: The administration of PGI2 stimulated the pregnant uterine muscle (in vitro). The oxytocic potency of PGE1-analog (ONO-802) was greatest, followed in order by that of PGF2 alpha and PGI2. The effect of 5-lypoxygenase inhibitor (AA-861) on uterine contraction was greatest under the administration of LTC4, followed in order by PGI2, oxytocin, PGF2 alpha, LTD4 and ONO-802. The effect of AA-861 was greater under the simultaneous administration of LTD4/LTC4 and ONO-802 than under the simultaneous administration of oxytocin and ONO-802. Terbutaline exerted the inhibitory effect on each of the oxytocies within two minutes in all cases. Its inhibitory effect on the oxytocics was slight in the cases to which oxytocin or ONO-802 was administered. Changes in cyclic nucleotides in the bath medium were determined before and after the administration of each drug. When PGI2 was administered, both c-AMP and c-GMP increased and showed a pattern which was different from that for other oxytocics. This tendency was also observed when PGI2 and other drugs (terbutaline, ONO-802 and AA-861) were administered together.
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PMID:[A basic study of the oxytocic effect of prostacyclin on the uterine muscle in pregnant rats]. 353 66

The use of gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the early second trimester has been further investigated. Of 113 women between 12 and 16 weeks gestation, 93 (82%) aborted within 24 hours of the administration of 4.4 +/- 0.1 1 mg gemeprost pessaries. The mean induction-abortion interval was 881 +/- 31 minutes. Successful abortion was achieved in 16 of the remaining 20 women after a second course of gemeprost pessaries without the need for oxytocin supplementation. There were no serious complications. Crampy abdominal pain and vaginal bleeding started after 275 and 756 minutes respectively. Twenty-two (19%) patients did not require pain relief during treatment, but 90 (80%) required parenteral opiates. Vomiting and diarrhoea occurred in 16 (14%) and 23 (20%) cases respectively. The safe induction of therapeutic abortion in 96% of women using vaginal prostaglandin alone offers an acceptable alternative to surgical evacuation in the early second trimester.
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PMID:Prostaglandin-induced pregnancy termination: further studies using gemeprost (16,16 dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries in the early second trimester. 368 94

Antifertile effects of PGF2 alpha, PGE2, PGE1, sulprostone and other PGs were evaluated in different pregnancy models in rats, guinea pigs and rhesus monkeys and the underlying mechanisms of action were investigated. Quantitative and qualitative species differences and pregnancy stage dependency were recorded. Basic regulatory differences of the pregnant uterus seem to exist in these species. In early pregnant rats, abortifacient effects were based on luteolytic effects, independent of the PG used. The myometrium was found to be refractory to the injected PG as long as serum progesterone levels were kept high. By contrast, in guinea pigs after the luteoplacental shift of progesterone secretion (tested after day 40 p.c.) and in rhesus monkeys even before this shift (tested day 20 p.c.) abortifacient effects were found to be exerted by direct stimulation of the myometrium. Uterine stimulation was possible in the presence of any level of serum progesterone. The induction of uterine PG synthesis was probably of importance supporting the expulsion. The role of obvious tissue damage within the conceptus remained uncertain. In contrast to rats there seems to be a pre-existing PG-sensitivity of the pregnant myometrium in guinea pigs and primates. In guinea pigs sensitivity slightly increased for E- but not for F-type PG toward term. Oxytocin sensitivity was found to increase by a factor of more than 100 between days 23-63 of pregnancy. Time dependent changes in uterine receptivity to PG and oxytocin may be considered as a regulatory principle which might permit parturition to occur in the presence of progesterone as an evolutionary adaptation to a placental progesterone secretion which cannot be abolished. It was concluded that in the presence of already established gradual uterine responsiveness to PG (and Oxytocin) during gestation efficient blocking mechanisms for uterine PG-formation must exist in order to explain uterine quiescence. Almost complete resistance of pregnancy to oestrogen which exists in humans, monkeys and guinea pigs was considered as to be pharmacological evidence of such a mechanism. The principles of endocrine control of the myometrium and its pharmacology seem similar in guinea pig and primate pregnancy. The guinea pig might therefore provide a relevant model to study potential drug effects on the regulatory balance of the pregnant uterus and also to achieve a better understanding of human uterine physiology.
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PMID:Studies on the mechanism of action of antifertile PG in animal models. 385 89

In a study of 32 patients, there were 29 cases of intra-uterine fetal death and 3 cases of hydatidiform mole. The intravenous administration of either prostaglandin E1, E2 or F2 successfully induced labor in 29 out of the 32 cases. 2 patients delivered following additional intravenous oxytocin and there was 1 failure due to the development of upper limb cyanosis. Side-effects included vomitng, phlebitis, facial flushing, rigors, pyrexia and uterine hypertonus. The method confirms the high success rates reported previously but the incidence of side-effects was disturbing. It is emphasized that prostaglandin E1 was used during this original research trial when prostaglandins were 1st investigated clinically. Prostaglandin E1 has not been made available commerically.
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PMID:Induction of labour and abortion by intravenous prostaglandins in pregnancies complicated by intra-uterine foetal death and hydatidiform mole. 444

Clinical research has shown that prostaglandins (PGs) play an important role in every phase of human reproduction. The logical consequence of early basic biological research into PGs is the current interest in clinical evaluation of PGs as agents to induce labor and abortion and to stimulate menstruation. This is a review of the current literature dealing with PG research. Both PGF2alpha and PGE2 are known to induce labor at term when administered by intravenous infusion. Their relative effectiveness as compared to oxytocin has yet to be assessed. Intravenous infusion of PGE1, PGE2, and PGF2alpha will also induce abortion. Current research is being directed toward finding more practical methods of administration than continuous intravenous infusion. There is hope that PGs will be able to be used as a once a month contraceptive administered at the time of expected menstruation following exposure and a possible unwanted pregnancy. The exact mechanism of action of PGs on smooth muscle is still largely unknown. The differences in response of a specific muscle to different PGs have also not received much research attention. Little is known, for example, regarding the action of PGs on the cervix as opposed to the rest of the uterus. Particularly unknown is the mechanism of action of PGs at the molecular level. In most of the situations studied, PGs seem to stimulate adenyl cyclase activity and cyclic adenosine monophosphate formation or accumulation.
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PMID:Developing applications of prostaglandins in obstetrics and gynecology. 462 50

A review of early research (up through 1970) on prostaglandins (PGs) is presented. Their chemical structure and classification based on their ring-structure is detailed as well as various analytic methods of mammalian tissues and body fluids. For clinical use PGE1 and 2, PGF2alpha and PGA1 are the most significant ones because of their properties. PGs have many physiological activities encompassing many organ systems. Their pharmacological actions include: 1) stimulation of nonvascular smooth muscle; 2) peripheral vasodilation (excluding PGFs which cause vasoconstriction); 3) inhibition of lipolysis; 4) inhibition of platelet aggregation; 5) inhibition of gastric peristalsis and gastric juice secretion; 6) bronchodilation; and 7) inhibition of spontaneous CNS activity. The level of PGEs in semen is closely related to the degree of fertility; normally fertile men have 55 mcg PGE/ml and never less than 11 mcg/ml. Current studies are under way on the effect of PGE in artificial insemination of sperm of subfertile men. PGF2alpha and PGE2 stimulate menstruation and uterine contraction; other PGs inhibit uterine contraction. PGs from semen have a role in sperm transport and possibly act on fallopian tube motility aiding sperm capacitation, and ovum retention and transport. Early trials with PGs point to a possible action as an abortifacient, as a once-a-month contraceptive, or a postconception contraceptive agent. PGF2alpha is found in variable concentrations in maternal blood during contraction of the pregnant uterus; levels increase as labor progresses. PGs have been used for labor induction, for induction of abortion and in mole pregnancy. Given as a constant intravenous infusion they produce regular contractions leading to natural expulsion of the fetus and causing very few side effects in the woman with no adverse effects on the fetus. PGs' action compares favorably with that of oxytocin and is preferable for labor induction in certain pregnancy complications. PGE1 and 2 have a stronger effect than PGF2alpha, hence can be used in smaller dosage and cause fewer adverse effects.
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PMID:[Prostaglandins in gynecology and obstetrics]. 505 16

This in vitro study examines the possibility that the E prostaglandins (PGEs) supplement the action of syntocinon on human muscle strips. 11 strips of upper segment myometrium removed from 10 pregnant patients (17-40 weeks gestation) for various reasons were analyzed. The human myometrium at term responded to a minimum concentration of 0.01-0.05 mcg syntocinon and 1-5 ng PGE1 or PGE2 in the 5 ml bath, while the midtrimester myometrium responded to 0.2-1 mcg syntocinon and 2-20 ng PGE1 or PGE2. These results show a 20 times increase in myometrial sensitivity to syntocinon and a 2-4 fold increase in sensitively to PGE1 or PGE2 at term as compared to the midtrimester. A syntocinon dose given immediately following a dose of PGE exhibited a response greater than that elicited by the same dose of syntocinon prior to the PG; this sensitizing effect of PG was observed in both term and midtrimester myometrium. The enhancement effect was observed in the increased duration of syntocinon response or as an increase in amplitude of response or a combination of these, the effect lasting for as long as 90 minutes after the PGE dose had been washed out of the bath. These findings led to the hypothesis that during the parturition process, endogenous PGs act as mediators which sensitize the uterine muscle to circulating oxytocin. The physiological implication of this enhancement effect is that undesirable side effects (vomiting, diarrhea) associated with PG infusion may be reduced or even eliminated when the PG-syntocinon method is used.
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PMID:Interaction of E prostaglandins and syntocinon on the pregnant human myometrium. 555 14


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