UNIPROT:P01178 - FACTA Search

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

The overall rate of induction of labor in the United States in 1993 was 134 per 1,000 live births, or over 527,000 of the four million births that occur annually in the United States. Indications for labor induction include postdate pregnancy, premature rupture of membranes (PROM), and maternal medical complications, such as diabetes mellitus and pregnancy-induced hypertension. This article briefly reviews common indications for induction of labor and the importance of cervical ripening. It then addresses methods used to hasten cervical ripening and to induce labor, ranging from the more "natural" and noninvasive methods, such as nipple stimulation, to the newest commercially available formulation of prostaglandin. Methods well documented in the scientific literature, as well as those commonly used but less well studied, are included. Although one may argue about the "invasive" nature of these methods, they are addressed, in general, from the most natural methods to the latest pharmacologic methods, and they include the following: sexual intercourse, nipple/breast stimulation, herbal preparations, homeopathic solutions, castor oil, enemas, acupuncture, membrane sweeping or stripping, mechanical dilation (balloon catheters, laminaria, and synthetic osmotic dilators), amniotomy, and pharmacologic hormonal preparations (prostaglandin E2, oxytocin, misoprostol, mifepristone, and relaxin).
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PMID:Methods of cervical ripening and labor induction. 910 14

The effect of intracerebroventricular (ICV) injections of synthetic human or rat relaxin (25 or 250 ng) on the distribution of Fos detected immunohistochemically in the rat forebrain was investigated. Following ICV relaxin, many Fos-positive neurons were observed in the periphery of the subfornical organ, dorsal part of the organum vasculosum of the lamina terminalis, throughout the median preoptic nucleus, supraoptic nucleus and hypothalamic paraventricular nucleus. Such effects did not occur following ICV injection of artificial cerebrospinal fluid or the separated A and B chains of relaxin, nor following the intravenous injection of 250 ng of relaxin. Both vasopressin and oxytocin containing neurons identified immunohistochemically in the supraoptic and paraventricular nuclei exhibited Fos following ICV relaxin, and many neurons in the medial parvocellular part of the paraventricular nucleus contained Fos. The results indicate that centrally administered relaxin may increase neuronal activity in regions of the hypothalamus and lamina terminalis which are associated with cardiovascular and body fluid regulation and oxytocin secretion.
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PMID:Distribution of Fos immunoreactivity in the lamina terminalis and hypothalamus induced by centrally administered relaxin in conscious rats. 922 54

These studies were designed to determine whether continuous i.v. infusion of increasing dosages of porcine relaxin during late pregnancy in beef heifers would influence circulating blood concentrations of relaxin, progesterone and oxytocin, and time of onset of parturition. Beef heifers were bred by artificial insemination and, on Day 277, fitted with indwelling jugular cannulas for hormone infusion and blood sampling from Day 277 to Day 286. Intravenous infusion of purified porcine relaxin (pRLX, 3000 U mg-1) was started in heifers (n = 8) at increasing dosages (200 U h-1 on Days 277 and 278, 300 U h-1 on Days 279 and 280, 500 U h-1 on Day 281, 600 U h-1 on Day 282, and 700 U h-1 on Days 283-286). Phosphate-buffered saline (PBS, 10 ml h-1) was infused during these same times to control animals (n = 6). Relaxin treatment steadily increased the circulating plasma concentration of immunoreactive relaxin to more than 120 ng ml-1 compared with less than 0.5 ng ml-1 in PBS-treated controls. Relaxin infusion in increasing dosages over the treatment time was associated with a significant decrease (P < 0.01) in plasma progesterone concentration compared with the PBS controls. The rate of change in progesterone levels between pRLX and PBS groups differed (P < 0.05) at 300 U h-1, 600 U h-1 and 700 Uh-1 dosage intervals, respectively. Plasma levels of oxytocin at 4 h intervals remained similar (P > 0.05) during the pretreatment period and throughout continuous infusion of pRLX and PBS. Mean concentrations of oxytocin in PBS control heifers peaked at 0.95 pgml-1 during the corresponding infusion of 700 Uh-1 pRLX, which peaked at 0.77 pgml-1. Although continuous i.v. infusion of relaxin resulted in a decrease in circulating blood levels of progesterone, it did not significantly reduce the interval between the beginning of pRLX treatment and parturition compared with the PBS-infused control heifers. These results indicate that continuous i.v. infusion of high levels of porcine relaxin resulted in a decrease in progesterone secretion in late pregnant beef heifers.
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PMID:Continuous infusion of relaxin on periparturient progesterone, oxytocin and relaxin plasma concentrations and time of parturition in beef heifers. 923 Dec 43

Relaxin, administered parenterally, has been shown to increase the release of oxytocin (OT) into the circulation and increase the firing rate of OTergic neurons. The objective of the present study was to determine if relaxin administration can result in the expression of a transcription factor, suggesting that it alters transcriptional activity within OTergic neurons at the level of the hypothalamus. Primigravid rats were ovariectomized and a jugular cannula was inserted on day 11 of gestation (g11). Pregnancy was maintained by implanting 17 beta-estradiol and progesterone caplets subcutaneously at the time of ovariectomy. At gl9, rats were challenged with intravenous relaxin or isotonic saline and the brains were removed for study. Immunohistochemistry was performed on coronal brain sections, utilizing Fos as a marker of cellular activation. In the group receiving relaxin, Fos-like immunoreactivity (Fos-IR) was abundant only in the supraoptic (SON) and paraventricular nuclei (PVN) of the hypothalamus as well as in the subfornical organ (SFO). In contrast, Fos-IR in the group given isotonic saline was lacking in these three brain regions. A double label study using antibodies against Fos and OT demonstrated that a majority of the Fos-labeled cells in the hypothalamus were OTergic. Because Fos can act as a transcription factor, we interpret these data to indicate that transcription within OTergic cells is altered following relaxin administration, with abundant Fos-IR being limited to the SON and PVN of the hypothalamus and the SFO during late pregnancy in the rat.
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PMID:Relaxin-induced expression of Fos in the forebrain of the late pregnant rat. 925 17

1. Glibenclamide, a blocker of ATP-sensitive potassium channels, has been shown to antagonize relaxin as a uterine relaxant in the rat in vivo but not in vitro. The aim, therefore, was to investigate whether the discrepancy between the two studies was a consequence of differences in (1) muscle layers, (2) hormonal conditions or (3) spasmogens utilized. Relaxin was compared with salbutamol and levcromakalim. 2. Relaxin was of similar potency as a uterine relaxant against oxytocin (0.2 mM)-induced spasm with tension measured in the circular or longitudinal muscle layers. Glibenclamide (10 microM) did not antagonize relaxin or salbutamol in these preparations but greatly antagonized levcromakalim (91-fold). Relaxin was a relaxant of tension activated by transmural electrical stimulation in uteri from rats that had been ovariectomized, although the maximal effect was only 30 +/- 15%, and in uteri from rats that had been treated with 17 beta-estradiol benzoate. Glibenclamide was not an antagonist of relaxin in the latter preparation but did antagonize levcromakalim (118-fold). Relaxin also inhibited spontaneous phasic tension development in uteri from ovariectomized rats but again was not antagonized by glibenclamide. 3. Because relaxin was not antagonized by glibenclamide under any of these various conditions, it would appear that the in vivo-in vitro discrepancy in the antagonism of relaxin by glibenclamide is not attributable to the effects of different muscle layers, hormonal conditions or spasmogens. It may be that the mechanism of action of relaxin or glibenclamide or both differs between in vivo and in vitro preparations.
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PMID:Relaxin as a relaxant of the isolated rat uterus: comparison with its mechanism of action in vivo. 934 34

The effects of porcine relaxin were examined in urethane-anesthetized, lactating rats to clarify the actions of relaxin on basal levels and the pulsatile release of oxytocin during suckling. Baseline plasma oxytocin concentrations were 27.6+/-2.9 pM in unsuckled rats. They were significantly increased in rats after the onset of suckling (34.5+/-2.4 pM) compared with unsuckled animals. Oxytocin concentrations were increased further during reflex milk ejection (41.2+/-2.7 pM). Treatment with porcine relaxin (5 microg in 0.1 ml saline) caused a significant (p < 0.05) increase in plasma oxytocin compared with pretreatment concentrations or saline injection in all three groups. Frequent blood samples were taken before and during milk ejection to confirm pulsatile oxytocin associated with reflex milk ejection. Short-lived (5-10-sec) pulses with peak concentrations of oxytocin 392.4+/-122.1 pM were observed shortly before or at the time of the peak rise in intramammary pressure associated with reflex milk ejection. Relaxin (5 microg i.v.) completely suppressed the pulsatile release of oxytocin. These data suggest that relaxin increases basal secretion of oxytocin but inhibits the pulsatile secretion associated with reflex milk ejection.
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PMID:Relaxin inhibits the pulsatile release of oxytocin but increases basal concentrations of hormone in lactating rats. 954 28

The effects of cAMP on the oxytocin-stimulated increase in phosphatidylinositide turnover and the possible pathways involved were investigated in a human myometrial cell line (PHM1-41) and in COS-M6 cells overexpressing the oxytocin receptor. Preincubation with chlorophenylthio-cAMP (CPT-cAMP), forskolin, or relaxin inhibited oxytocin-stimulated phosphatidylinositide turnover in PHM1-41 cells, and the inhibition was reversed by H-89, a relatively specific protein kinase A inhibitor. Both CPT-cAMP and transiently expressed protein kinase A catalytic subunit inhibited stimulation by oxytocin and carbachol of [3H]inositol 1,3,4-trisphosphate formation in COS-M6 cells expressing oxytocin or muscarinic M1 receptors, respectively. CPT-cAMP also inhibited phosphatidylinositide turnover stimulation by endothelin-1 in PHM1-41 cells, further demonstrating the generality of the cAMP-inhibitory mechanism. Since G betagamma activation of phospholipase Cbeta2 (PLCbeta2) is a suggested target of protein kinase A, the possibility that the oxytocin receptor couples to PLCbeta2 via G alpha(i)G betagamma activation was explored. Western blot analysis of PHM1-41 cells and COS-M6 cells detected PLCbeta1 and PLCbeta3, but not PLCbeta2. In PHM1-41 cells, pertussis toxin reduced the oxytocin-stimulated increase in [3H]inositol 1,3,4-trisphosphate by 53%, and this was reversed completely by H-89. Thus, the inhibitory effect of pertussis toxin may result from an indirect effect of cAMP elevation. These data suggest that receptor/G alpha(q)-coupled stimulation of PLCbeta1 or PLCbeta3 can be inhibited by cAMP through a phosphorylation mechanism involving protein kinase A that does not involve PLCbeta2. In smooth muscle, this mechanism could constitute potentially important cross-talk between pathways regulating contraction and relaxation.
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PMID:Evidence for inhibition by protein kinase A of receptor/G alpha(q)/phospholipase C (PLC) coupling by a mechanism not involving PLCbeta2. 956 32

The effects of porcine relaxin on arterial blood pressure, heart rate, and the release of vasopressin and oxytocin were investigated in homozygous diabetes insipidus (di/di) Brattleboro and Long-Evans rats. Acute iv injection of relaxin (5 microg) caused a significant increase in mean arterial, systolic and diastolic blood pressures in Long-Evans rats compared with control injections of saline, but had no pressor effect in Brattleboro rats. Circulating concentrations of vasopressin were also significantly elevated above baseline in the Long-Evans rats 1 min after relaxin treatment, but remained undetectable in the relaxin-treated Brattleboro rats. Relaxin increased heart rate in both groups of animals 4 min after injection. The chronotropic effect of relaxin was, however, attenuated in the Brattleboro rats. Intravenous relaxin injection also caused a significant increase in plasma oxytocin concentrations 5 min posttreatment in both the Long-Evans and Brattleboro rats. The change in plasma oxytocin above basal concentrations was significantly greater in Brattleboro rats compared with Long-Evans controls. The data in this study demonstrate that iv relaxin increases heart rate, but not arterial blood pressure in Brattleboro rats. Furthermore, the relaxin-induced release of oxytocin in Brattleboro rats does not result in an acute pressor response.
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PMID:The cardiovascular effects of porcine relaxin in Brattleboro rats. 974 37

The importance of the localization of protein kinase A (PKA) to the plasma membrane for cAMP-mediated inhibition of phosphatidylinositide turnover was tested in an immortalized pregnant human myometrial (PHM1-41) cell line, and the putative A kinase anchoring protein (AKAP) involved was identified. Preincubation in PHM1-41 cells with chlorophenylthio-cAMP (CPT-cAMP), forskolin, or relaxin inhibited the ability of oxytocin to stimulate phosphatidylinositide turnover. The addition of a peptide that specifically disrupts interactions of PKA RII subunits with AKAPs (S-Ht31) reversed the effects of these agents, whereas a control peptide was ineffective. The pharmacology of S-Ht31 on this particular membrane event was further characterized. A 10-min incubation with S-Ht31 at a concentration of 1 microM completely reversed the inhibitory effect of relaxin on phosphatidylinositide turnover. S-Ht31 inhibited cAMP-stimulated PKA activity in PHM1-41 cell plasma membranes and decreased the concentration of PKA. Overlay analysis detected a single AKAP of approximately 86 kDa associated with the plasma membrane of PHM1-41 cells, suggesting that the association of PKA with this AKAP is important for the cAMP inhibitory mechanism. The mol wt of this AKAP was similar to that of an AKAP associated with the plasma membrane in the human brain, AKAP79. Antibodies against AKAP79 recognized a band at 86 kDa in purified plasma membranes from the PHM1-41 cells, indicating similar determinants in these proteins. These data suggest that PKA is anchored to the myometrial plasma membrane through association with an AKAP similar to AKAP79, and that this anchoring is required for the cAMP-mediated inhibition of phosphatidylinositide turnover in PHM1-41 cells.
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PMID:Protein kinase A anchoring to the myometrial plasma membrane is required for cyclic adenosine 3',5'-monophosphate regulation of phosphatidylinositide turnover. 1053 45

The existence of numerous neuropeptides in milk, in concentrations that exceed those in maternal plasma, is well established. It is still unclear whether these neuropeptides are produced by the mammary gland or that the gland concentrates them from the general circulation. In this study, we have examined the possibility that the genes of these neuropeptides are expressed in the rat mammary gland. RNA was extracted from the mammary glands of female rats during different stages of reproduction as well as from other tissues such as hypothalami, pancreas, pineal glands, small intestine, and ovaries. Following RT reaction, the resulting cDNA were amplified by radioactive PCR using specific oligonucleotide primers. We have used specific primers for the following neuropeptides: galanin, somatostatin, vasoactive intestinal peptide, TRH, GH-releasing hormone, cholecystokinin, neurotensin, oxytocin, and relaxin. We have also used primers for serotonin N-acetyl-transferase, the enzyme that is involved in melatonin biosynthesis. The ribosomal protein S-16 served as an internal control. Among all the neuropeptides that have been examined, somatostatin was the only one that was found to be expressed in the mammary gland. Somatostatin was expressed in the mammary gland of lactating rats, but not of virgin rats. Expression of the somatostatin gene was confirmed by Southern blot analysis and by sequencing of the PCR products. Immunohistochemical studies demonstrated somatostatin immunoreactivity in the epithelial cells that compose the secretory alveoli and in the secretory material. In addition, we have found that the mammary glands of the lactating rat express the PC-1 proteinase gene that process prosomatostatin to generate somatostatin-14, but do not express furin, the enzyme that is responsible for somatostatin-28 production. This finding substantiates previous studies that demonstrated that only somatostatin-14 is present in milk. The finding that most of the neuropeptides, examined by RT-PCR, are not expressed by the mammary gland suggest that these neuropeptides are actively concentrated by the mammary glands from the general circulation. The GnRH gene has been previously demonstrated to be expressed in the mammary gland, and in this study somatostatin was the only neuropeptide that was found to be produced by the mammary gland. The observation that only a small portion of the neuropeptides that are present in milk are being produced by the lactating mammary gland suggest that these neuropeptides have important functions in the biology of the suckling neonate and probably also in the development and function of the breast.
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PMID:Selective expression of neuropeptides in the rat mammary gland: somatostatin gene is expressed during lactation. 1057 58

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