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)

The effect of extended infusions of highly purified porcine relaxin on uterine activity was tested in vivo in conscious unrestrained rats. Relaxin was found to inhibit oxytocin- and prostaglandin F2 alpha-induced uterine contractions in estrogen-treated ovariectomized rats as well as spontaneous contractions in both estrogen-treated and steroid-untreated ovariectomized rats. The inhibition of both induced and spontaneous uterine contractions was more effective in the early phases of relaxin infusion than after prolonged exposure to the hormone. However, this desensitization was not complete, and the inhibition was effective even with extended (up to 72 h in the oxytocin experiments) infusion of relaxin. The results indicate that relaxin may be important in controlling uterine activity in the rat near the end of gestation, and that estrogen priming in ovariectomized rats is not necessary for relaxin to exert its biological effects.
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PMID:Effects of relaxin on in vivo uterine contractions in conscious and unrestrained estrogen-treated and steroid-untreated ovariectomized rats. 694 25

Plasma relaxin concentrations were measured hourly by radio immunoassay in 4 pregnant mares from 11 days before until 4 days after natural foaling. Pre-partum levels ranged from 4 to 7 ng/ml without any surge until the second stage of labour when they increased rapidly to about 11 ng/ml. In 3 of these mares, relaxin activity declined immediately after the expulsion of the placenta and was below detectable levels within 36 h. In the other mare relaxin activity did not fall until after the mechanical removal of the placenta 7 h after foaling. Eight mares were induced to foal by the administration of oxytocin. In 5 out of 6 mares induced with a single i.v. injection of 40 i.u. plasma relaxin increased following injection and peaked at 17 ng/ml shortly after foaling and expulsion of placenta. Activity then rapidly declined. In the 6th mare, which retained the placenta, relaxin activity did not decrease after foaling. Administration of more oxytocin to this mare after foaling resulted in a further increase in plasma relaxin activity, but oxytocin treatment of other mares after placental delivery failed to elicit a similar increase. In the 7th mare 2 i.v. injections of 40 i.u. oxytocin induced a relaxin concentration of 34 ng/ml whereas in the remaining mare one i.m. injection of 40 i.u. oxytocin led to a relaxin profile similar to that in naturally foaling mares. Oxytocin may therefore be responsible for the increased secretion rate of relaxin at foaling. These data support the concept that the placenta is the sole significant source of relaxin in the pregnant mare.
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PMID:Relaxin activity in foaling mares. 696 2

Myometrial activity was abolished abruptly but reversibly in 4 out of 5 ewes by the intravenous injection of 1 mg (500 GPU) porcine relaxin. Recovery began only after about 90 min and was not complete until 3-4 h after the injection. During the relaxin-induced inhibition the myometrium responded to oxytocin administered intravenously in doses of 250 mU. One ewe received intrauterine infusions of 2.5 and 5.0 microgram PGF-2 alpha per min during the period of relaxin inhibition: the former dose evoked a slight, and the latter a marked, response from the myometrium. The rate of rise of intrauterine pressure and the mean amplitude of pressures cycles were significantly depressed at 1, 1.5 and 2 h after the relaxin injection.
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PMID:Relaxin inhibits myometrial activity in the ovariectomized non-pregnant ewe. 720 86

Relaxin in doses of 5 microgram i.v. completed but reversibly abolishes "spontaneous' myometrial activity in anaesthetized ovariectomized rats. Similar levels of myometrial activity, evoked in oestrogen-treated rats (which normally have quiescent uteri) by infusions of oxytocin or prostaglandin F2alpha (PGF2alpha), were also reduced to complete quiescence by relaxin in small doses. However when spontaneous myometrial activity in untreated ovariectomized rats was slightly stimulated by oxytocin the uterus became completely refractory to the inhibitory effects of relaxin even at doses of 50 microgram. Relaxin was also ineffective in reducing myometrial activity in similar rats during intra-arterial infusion of PGF2alpha. It is suggested that the ability of relaxin to inhibit uterine smooth muscle during exogenous stimulation is oestrogendependent.
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PMID:Inhibition of oxytocin-or prostaglandin F2alpha-driven myometrial activity by relaxin in the rat is oestrogen-dependent. 725 1

The stimulating effect of some drugs on the ripening of the uterine cervix in rats was studied by measuring the wet weight of the uterine cervix and by both light and electron microscopy in nonpregnant castrated and pregnant conditions. Since the light and electron microscopic findings after estrogen (E) administration to castrated rats were similar to those found in the uterine cervix of rats at the end of pregnancy, it was concluded that E (E2 greater than or equal to E3 greater than or equal to E1) plays a major role in the ripening mechanism. It was also found that DHA-S, progesterone and relaxin had stimulating effects on cervical ripening. Oxytocin and PG (PGE2 greater than PGF2 alpha) showed the ripening activity only in pregnant condition. Moreover, oxytocin, PGE2 and PGF2 alpha potentiated the estrogen action. The effects on the increase in wet weight of the uterine cervix and microscopic findings due to DHA-S were different from E in castrated rats. It is therefore postulated that the effect of DHA-S might be mainly due to the secondary increase in E converted from DHA-S in the ovary and, in addition, to a direct effect of this medicament on the uterine cervix. There was essentially no difference in ultrastructure between the cervix of control (nonpregnant, castrated or pregnant) rats and that of rats treated with HCG, isoxsuprine hydrochloride, dihydroergotoxine, diazepam or n-butylscopolammonium bromide.
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PMID:Effects of some drugs on ripening of uterine cervix in nonpregnant castrated and pregnant rats. 726 63

The novel finding that relaxin has an action on the brain was first published in 1984. Since then, it has been shown that exogenous relaxin affects the release of a number of hypothalamo-pituitary hormones and has a robust pressor action. In this paper, we review the accumulating evidence that relaxin affects the release of oxytocin and vasopressin by an action at the level of the brain. The potential mechanisms of this central action are discussed and the evidence presented for the interaction between relaxin and the forebrain angiotensin-II system. Furthermore, we articulate the possible physiological influences of relaxin on the changes in cardiovascular function that occur during pregnancy.
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PMID:The emerging concept of relaxin as a centrally acting peptide hormone with hemodynamic actions. 755 Feb 88

Relaxin is known for its function in parturition and has been suggested to participate in the regulation of blood pressure, heart rate, and the release of neuropeptides such as oxytocin and vasopressin. Consistent with the physiological roles of relaxin, high affinity relaxin receptors have been demonstrated in the rat uterus, brain, and cardiac atrium. Here we report the binding and cross-linking of a biologically active, 32P-labeled human relaxin to a human uterine cell line and primary rat atrial cardiomyocytes. Relaxin binding to the human uterine cells consisted of a single class of high affinity sites (Kd = approximately 0.44 nM) with approximately 1082 +/- 62 binding sites/cell. Binding and cross-linking of relaxin to the human uterine cells and rat atrial cardiomyocytes followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis revealed that the putative relaxin receptor showed a major component with an apparent M(r) greater than 220 kilodaltons and a minor component of approximately 36 kilodaltons, and was not disulfide linked. The binding and cross-linking of [32P]relaxin could be displaced by unlabeled relaxin in a concentration-dependent manner, but not by a 1000-fold molar excess of insulin, insulin-like growth factor I (IGF-I), or IGF-II. These data suggested that the relaxin receptor was similar in size but distinct from the insulin, IGF-I, and IGF-II receptors.
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PMID:Binding and cross-linking of 32P-labeled human relaxin to human uterine cells and primary rat atrial cardiomyocytes. 766 57

Situations related to labor and delivery that may require drug therapy are discussed, and treatment options are reviewed. The goal of labor induction and augmentation at term is to facilitate vaginal delivery of a healthy infant. The primary uterine stimulant used for this purpose is oxytocin. Low-, intermediate-, and high-dose protocols have been reported; augmentation requires approximately half as much oxytocin as induction does. Mifepristone has also been used for labor induction. Prostaglandins are the primary agents used for cervical ripening, but oxytocin, relaxin, and mifepristone have also been used. Mechanical dilators are available for cervical dilation, which may be necessary when prostaglandins are contraindicated. Oxytocin is the drug of choice for preventing postpartum hemorrhage; if it is not effective, methylergonovine or carboprost may be used to control the hemorrhage. Labor induction during the midtrimester may be necessary because of obstetrical or medical complications or fetal death. These situations call for aggressive dosing of uterine stimulants (e.g., high-dose oxytocin, intravaginal dinoprostone suppositories, carboprost, mifepristone). Drug therapy may be required for labor induction or augmentation, cervical ripening or dilation, and prevention or control of postpartum hemorrhage. Oxytocin is the most commonly used agent for labor induction or augmentation and for prevention of postpartum hemorrhage; prostaglandins are frequently used for cervical ripening. Aggressive dosing of uterine stimulants is required when labor must be induced during the midtrimester.
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PMID:Drug therapy during labor and delivery. 784 4

The initiation of a complex cascade of events resulting in the delivery of a healthy newborn appears to involve the integrated actions of the fetus, mother and the placenta. Many putative factors have already been extensively reviewed. Instead of concentrating on the action of estrogen and progesterone, the role of regulators of myometrial activity such as prostaglandins as well as the fetal pituitary-adrenal system, oxytocin, corticosteroids, leukotrienes, platelet activating factor, endotoxin and cytokines to name a few, will be discussed. Nevertheless, there is an increasing weight of evidence suggesting that many of the above agonists converge upon a final pathway of prostaglandin production which subsequently increases myometrial responsiveness. Prostaglandins are involved at levels of myometrial regulation such as myometrial gap junction formation, intracellular calcium flux modulation, synchronisation of myometrial contraction via interaction with oxytocin thus having stimulatory effects on uterine contractility, as well as cervical maturation (via PGE2). Importantly, there has been clinical benefit of a more thorough understanding of the physiology of myometrial regulation at the time of partuition. The approach to the treatment of preterm delivery has improved, eventhough the exact mechanism(s) and cause(s) of this phenomenon remain an enigma. Current tocolytic therapy is not generally prophylactic but commences after labour, contractions and cervical dilatation are underway. Key regulatory pathways have been pin-pointed that present opportunity for tocolysis including:-c-AMP inhibition of contraction by beta-mimetic agents, inhibition of calmodulin-calcium function, inhibition of calcium influx by calcium channel blockers, inhibition of prostaglandin production, modulation of myometrial function by peptide hormones or antagonists (e.g. relaxin, VIP and oxytocin antagonists).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maintenance of high risk pregnancies: role of prostaglandins and other mediators. 784 15

Pregnant rats were ovariectomized (or sham-ovariectomized) on days 17, 18 or 21 of pregnancy and oestradiol-17 beta and progesterone were replaced. Prepartum oxytocin concentrations were significantly lower in ovariectomized steroid-treated rats than in intact controls, and on day 21 of pregnancy injection of relaxin into acutely ovariectomized rats significantly increased plasma oxytocin concentrations. During parturition, injection of the opioid antagonist naloxone induced significant increases in plasma oxytocin concentration compared with saline-injected rats. The naloxone-induced increase was significantly less in ovariectomized steroid-treated rats than in rats with intact ovaries, indicating that endogenous opioid activity is less in ovariectomized rats than in intact rats. The progress of parturition in the ovariectomized steroid-treated rats was severely disrupted compared with sham-ovariectomized rats despite similar plasma oxytocin levels at the birth of pup number 2; this disruption was not overcome by injection of naloxone or by the consequent increase in oxytocin secretion, indicating deficient preparation of the uterus and birth canal in the absence of relaxin. We conclude that the decreased oxytocin concentrations prepartum, the prolongation of parturition and the decrease in opioid tone in ovariectomized steroid-treated rats may be partly due to a lack of relaxin produced by the ovary.
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PMID:Endogenous opioid regulation of oxytocin release during parturition is reduced in ovariectomized rats. 785 84


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