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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, the effect of 14-deoxyandrographolide (14-DAP) on calcium channel-dependent rat uterine smooth muscle contraction was evaluated. Using a tissue bath preparation, 14-DAP was able to reduce the contractile response to 0.3 and 3.0 mm of CaCl(2), with an IC(50) of 1.24 +/- 0.23 x 10(-5) m and 5.94 +/- 0.29 x 10(-5) m, respectively. 14-DAP shifted the CaCl(2) cumulative dose response curve to the right, increasing the EC(50) from 2.08 +/- 0.20 x 10(-4) m to 4.22 +/- 0.22 x 10(-4) m (5 micrometer 14-DAP) and 2.5 +/- 1.0 x 10(-3) m (50 micrometer 14-DAP). In order to determine if 14-DAP had any effect on intracellular calcium, the relaxant response to 14-DAP following contraction by oxytocin, PGF(2alpha) and vanadate in Ca(+2)-free solution was compared with that of isoproterenol and phenylbutazone. While isoproterenol and phenylbutazone relaxed the smooth muscle in a dose-dependent manner, 14-DAP did not have any effect on either the oxytocin, PGF(2alpha) or vanadate-induced smooth muscle contraction. Based on these data, it appears that 14-DAP is an uterine smooth muscle relaxant which produces a selective blockade of voltage operated calcium channels.
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PMID:Effect of 14-deoxyandrographolide on calcium-mediated rat uterine smooth muscle contractility. 1459 78

In twin pregnancies, the use of beta-adrenergics is associated with a significantly higher incidence of cardiovascular complications, and calcium channel blockers as well as oxytocin antagonists currently appear as first line agents. After extreme preterm delivery of the first twin and in selected patients, the birth of second twin may be delayed with a mean gain of 10-50 days. In cases of symptomatic placenta previa with mild-to-moderate bleeding, tocolytic agents may be associated with a prolongation of pregnancy and increased birth weight without significant impact on frequency or severity of bleeding. Calcium channel blockers are the drugs of choice in the event of diabetes. Indomethacin is a potent tocolytic, in particular in patients with polyhydramnios. However, it may cause oligohydramnios, premature closure of the ductus arteriosus and intrauterine fetal death when high doses are administered for a duration exceeding 48 to 72 hours, particularly beyond 32 weeks' gestation. The neonatal complications of indomethacin occur frequently. Tocolysis appears to reduce the failure rate of external cephalic version at term.
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PMID:[The therapeutic role of tocolysis]. 1496 18

Tocolytic agents are drugs designed to inhibit contractions of myometrial smooth muscle cells. Such an effect has been demonstrated in vitro or in vivo for several pharmacological agents, including beta-adrenergic agonists, calcium channel antagonists, oxytocin antagonists, NSAIDs and magnesium sulfate. However, the aim of tocolysis is not only to stop uterine contractions or to prevent preterm delivery, but to prevent perinatal morbidity and mortality associated with preterm birth. The achievement of this goal has not yet been clearly demonstrated for any of the drugs available, and the use of tocolytic agents may appear controversial. Therefore, it is important to avoid maternal and fetal toxicity when tocolytic agents are used. During pregnancy, all steps of drug pharmacokinetics are altered. Absorption of drugs administered orally is limited because of delayed stomach emptying and reduced intestinal motility. The volume of distribution of drugs is increased. The metabolic activity of the liver is increased, accelerating the metabolism of lipophilic drugs. Renal filtration is increased, leading to enhanced renal elimination of water-soluble drugs. These modifications are generally responsible for reduced plasma concentration and reduced half-life of most drugs. These specific modifications have to be taken into account when using a drug in pregnant women. The aim of this review is to provide the reader with pharmacological data about drugs currently used to treat preterm labour. Such data in pregnant women may affect the choice of optimal drug dosage and route of administration.
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PMID:Pharmacokinetics of tocolytic agents. 1550 82

In article the fetal and neonatal side effects of tocolytic agents were presented. Described the cardiovascular; pulmonary metabolic, neurological and others complications during administration of magnesium sulfate, prostaglandin synthesis inhibitor, calcium channel blockers and oxytocin antagonist.
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PMID:[Effect of maternal pharmacological treatment of preterm delivery for neonatal condition]. 1553 51

Preterm birth is a major public health problem, affecting up to 10% of pregnancies. The cause of premature labour in humans is not known, although some risk factors have been identified. Currently it is not possible to predict which women will go into labour prematurely or deliver preterm. New possible methods for the detection of premature labour are the measurement of biochemical markers in cervical or vaginal secretions, the measurement of collagen in cervical tissue and the recording of electrical properties of contractions of the uterus. Agents used to prevent premature labour include beta-agonist drugs, magnesium sulphate, calcium channel blockers, nitric oxide donors and prostaglandin synthesis inhibitors. A new approach is the use of oxytocin antagonists. Premature labour is still not completely understood, but some advances are being made, arising from basic research.
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PMID:Detection and prevention of premature labour. 1573 84

The effects of the essential oil of Mentha pulegium L. (EOMP), a plant commonly known as "pennyroyal" or "poejo" that is used in folk medicine as an abortifaceant, were assessed on the isolated rat myometrium. Myometrial strips were stimulated with 10 nM oxytocin or 10 microM PGF (2alpha). EOMP (10 - 300 microg/mL) concentration-dependently and reversibly inhibited the amplitude of oscillatory contractions, being approximately 3-fold more active against contractions stimulated by oxytocin than those by PGF (2alpha) (IC (50) values of 45.7 +/- 5.6 microg/mL and 160.9 +/- 5.9 microg/mL , respectively), although the maximal inhibitory effect occurred at the same concentration (300 microg/mL ) in both cases. This action was shared by pulegone (30 - 300 microM), the principal component of the essential oil (IC (50) values of 21.8 +/- 2.1 microg/mL and 12.7 +/- 4.6 microg/mL , respectively). Nifedipine (30 nM - 30 microM) also abolished agonist-stimulated contractions, and was approximately twice and 12 times as potent as EOMP in inhibiting oxytocin- and prostaglandin F (2alpha) (PGF (2alpha))-stimulated contractions, respectively. In conclusion, our results show that the essential oil of the abortifaceant plant Mentha pulegium exerts an inhibitory effect on the contractile activity of the isolated rat myometrium. This oil shares a common effect with the voltage-dependent calcium channel (VDCC) blocker nifedipine, although ostensibly acting via a different mechanism. It thus appears that EOMP and pulegone do not exert direct toxic effects on the myometrium per se that would cause abortion, and other possibilities such as systemic metabolism of plant constituents may rather underlie the abusive use of Mentha pulegium in popular medicine.
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PMID:Inhibitory effects of the essential oil of Mentha pulegium on the isolated rat myometrium. 1577 May 40

The present study was undertaken to investigate the in vitro influence of mibefradil, a calcium channel blocker, and pinacidil, a potassium channel opener, on pregnant goat myometrial spontaneous rhythmic contractility and contractions induced with the agonist, oxytocin. Longitudinal strips from the distal region of uterus, collected from goats at midgestation, were mounted in an organ bath for recording isometric contractions. Mibefradil (10(-8)-10(-4) M) or pinacidil (10(-10)-10(-4) M), added cumulatively to the bath at an increment of 1 log unit, caused concentration-dependent inhibition of the spontaneous rhythmic contractions of isolated uterine strips. The rhythmic contraction was, respectively, abolished at 100 and 10 microM concentrations of mibefradil and pinacidil. In a concentration-dependent manner, mibefradil (1 and 10 microM) antagonized the contractions elicited with oxytocin (10(-5)-10(-2) IU). Pretreatment of uterine strips with glibenclamide (10 microM), a selective KATP channel blocker, caused a rightward shift of the concentration-response curve of pinacidil with a concomitant decrease in its pD2 value. Pinacidil (0.3, 1 and 3 microM), in a concentration-related manner, antagonized the oxytocin (10(-5)-10(-2) IU)-induced contractile response. The inhibition of spontaneous rhythmic contractions and antagonism of oxytocin-induced contraction by mibefradil in the pregnant goat myometrium may be related to the antagonism of voltage-dependent Ca2+ channels, while by pinacidil suggests that KATP channel could be a therapeutic target for tocolysis.
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PMID:Effects of calcium channel blocker, mibefradil, and potassium channel opener, pinacidil, on the contractile response of mid-pregnant goat myometrium. 1618 30

Oxytocin has been implicated in the modulation of somatosensory transmission such as nociception and pain. The present study investigates the effect of oxytocin on formalin-induced pain response, a model of tonic continuous pain. The animals were injected with 0.1 ml of 1% formalin in the right hindpaw and the left hindpaw was injected with an equal volume of normal saline. The time spent by the animals licking or biting the injected paw during 0-5 min (early phase) and 20-25 min (late phase) was recorded separately. Oxytocin (25, 50, 100 microg/kg, i.p.) dose dependently decreased the licking/biting response, both in the early as well as the late phases. The antinociceptive effect of oxytocin (100 microg/kg, i.p.) was significantly attenuated in both the phases by a higher dose of the non-selective opioid receptor antagonist naloxone (5 mg/kg, i.p.), MR 2266 (0.1 mg/kg, i.p.), a selective kappa-opioid receptor antagonist and naltrindole (0.5 mg/kg, i.p.), a selective delta-opioid receptor antagonist but not by a lower dose of naloxone (1 mg/kg, i.p.) or beta-funaltrexamine (2.5 microg/mouse, i.c.v.), a selective mu-opioid receptor antagonist. Nimodipine, a calcium channel blocker (1 and 5 mg/kg, i.p.) produced a dose-dependent analgesic effect. The antinociceptive effect of oxytocin was significantly enhanced by the lower dose of nimodipine (1 mg/kg, i.p.) in both the phases. Chronic treatment with oxytocin (100 microg/kg/day, i.p. daily for 7 days) did not produce tolerance in both the phases of formalin-induced pain response. The results thus indicate that oxytocin displays an important analgesic response in formalin test; both kappa- and delta-opioid receptors as well as voltage-gated calcium channels seem to be involved in the oxytocin-induced antinociception.
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PMID:Role of kappa- and delta-opioid receptors in the antinociceptive effect of oxytocin in formalin-induced pain response in mice. 1671 78

Tocolytic treatment of suspected preterm labour has been evaluated in at least 75 randomised controlled trials. These have been included in six Cochrane reviews. If the trials are poorly designed, such reviews may mislead or, at best, provide weaker evidence than those based on well-designed ones. The objective of this study was to compare the quality of the trials included in the Cochrane reviews of tocolytic therapy. Trial group sizes; the methods used by each trial to avoid selection, performance, attrition, and detection bias; and evidence that the statistical analysis plan was prespecified were abstracted from each Cochrane review. Except where noted, the judgement of the Cochrane reviewers was used. The number of trials graded A (sealed envelopes or third-party randomisation) for allocation concealment was as follows: beta-agonists 5/16, magnesium sulphate 9/23, oxytocin receptor antagonists 6/6, cox inhibitors 12/13, calcium channel blockers 9/12, and nitric oxide donors 5/5. The number blinding the intervention was as follows: beta-agonists 9/16, magnesium sulphate 2/23, oxytocin receptor antagonists 5/6, cox inhibitors 7/13, calcium channel blockers 0/12, and nitric oxide donors 1/5. The number reporting a sample size calculation was as follows: beta-agonists 2/16, magnesium sulphate 3/23, oxytocin receptor antagonists 6/6, cox inhibitors 4/13, calcium channel blockers 4/12, and nitric oxide donors 1/5. The mean sample size of each treatment group was as follows: beta-agonists 53, magnesium sulphate 41, oxytocin receptor antagonists 126, cox inhibitors 31, calcium channel blockers 43, and nitric oxide donors 46. Data on avoiding attrition bias (follow-up rates) are difficult to summarise because there is no agreed standard for 'complete follow up'. Data on avoiding detection bias (blinding of outcome assessments) appeared unreliable because reviewers reported this in different ways. In conclusion, the trials of oxytocin antagonists and beta-agonists were of the highest quality. There remains considerable scope for bias in many of the trials included in the current Cochrane systematic reviews of tocolytics.
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PMID:The quality of randomised trials of tocolysis. 1720 73

Nesfatin-1 is a recently identified satiety molecule detectable in neurons of the hypothalamus and nucleus of solitary tract (NTS). Immunohistochemical studies revealed nesfatin-1-immunoreactive (irNEF) cells in the Edinger-Westphal nucleus, dorsal motor nucleus of vagus, and caudal raphe nuclei of the rats, in addition to the hypothalamus and NTS reported in the initial study. Double-labeling immunohistochemistry showed that irNEF cells were vasopressin or oxytocin positive in the paraventricular and supraoptic nucleus; cocaine-amphetamine-regulated transcript or tyrosine hydroxylase positive in arcuate nucleus; cocaine-amphetamine-regulated transcript or melanin concentrating hormone positive in the lateral hypothalamus. In the brainstem, irNEF neurons were choline acetyltransferase positive in the Edinger-Westphal nucleus and dorsal motor nucleus of vagus; tyrosine hydroxylase positive in the NTS; and 5-hydroxytryptamine positive in the caudal raphe nucleus. The biological activity of rat nesfatin-1 (1-82) (100 nm) was assessed by the Ca(2+) microfluorometric method. Nesfatin-1 elevated intracellular Ca(2+) concentrations [Ca(2+)](i) in dissociated and cultured hypothalamic neurons. The response was prevented by pretreating the cells with pertussis toxin (100 nm) or Ca(2+)-free solution and by a combination of the L-type and P/Q-type calcium channel blocker verapamil (1 microm) and omega-conotoxin MVIIC (100 nm). The protein kinase A inhibitor KT 5720 (1 microm) suppressed nesfatin-1-induced rise in [Ca(2+)](i). The result shows that irNEF is distributed to several discrete nuclei in the brainstem, in addition to the hypothalamus and NTS reported earlier, and that the peptide interacts with a G protein-coupled receptor, leading to an increase of [Ca(2+)](i), which is linked to protein kinase A activation in cultured rat hypothalamic neurons.
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PMID:Nesfatin-1: distribution and interaction with a G protein-coupled receptor in the rat brain. 1762 99


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