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)

Synthesis and biological properties of [5-(N4,N4-dimethylasparagine)]oxytocin are reported. In this analogue, the hydrogens of the primary carboxamide moiety in the side chain of the asparagine residue in position 5 of the posterior pituitary hormone oxytocin have been replaced by two methyl groups. The protected nonapeptide intermediate was prepared by a stepwise procedure using solution techniques. The analogue possesses 4.60 +/- 0.03 units/mg (mean +/- SEM) uterotonic activity on the isolated rat uterine horn and 9.14 +/- 0.03 units/mg of avian vasodepressor activity. Moreover, it displays an identical intrinsic activity in the in vitro rat uterotonic assay as oxytocin, when tested in the presence of either 0.5 mM Ca2+ (standard assay conditions) or at reduced levels of Ca2+ (0.3, 0.15, and 0.05 mM). This result is significant in view of the proposed biologically active model of oxytocin, in which the side chain of the 5 position residue was assigned to contain an "active element" responsible for the intrinsic activity of the hormone when bound to the uterine receptor.
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PMID:Active-site studies of neurohypophyseal hormones: synthesis and pharmacological properties of [5-(N4,N4-dimethylasparagine)]oxytocin. 44 89

An antiserum to 13,14-dihydro-15-keto-prostaglandin F2alpha (PGF2alphaM) was prepared and a radioimmunoassay evaluated in various reproductive states. PGF2alphaM plasma concentration was 63.6 +/- 10.3 pg/ml (mean +/- SEM) in cycling women. The concentration fluctuated throughout the menstrual cycle and pregnancy, but no discernible patterns were noted. PGF2alphaM concentrations were elevated at the time of urea + oxytocin induced abortion (238 +/- 54 pg/ml) and during late stages of normal labor (352 +/- 107 pg/ml) but were not elevated during labor prior to 7 cm dilatation. Following intra-amniotic instillation of 5 mg of PGF2alpha tromethamine into the amniotic sac, PGF2alphaM concentration increased in the amniotic fluid. In the plasma of these patients there was an eighteenfold rise in plasma PGF2alphaM concentration compared to a 3.5-fold rise in PGF2alpha at 1 hour, suggesting changes in PGF2alphaM may be more easily detected than the parent compound. While PGF2alphaM may be a useful index of PGF2alpha production, it appears that PGF2alphaM is of little value in predicting the occurrence of uterine contraction.
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PMID:13, 14-dihydro-15-keto-prostaglandin F2alpha concentrations in human plasma and amniotic fluid. 45 60

Sensitive and highly specific RIAs for arginine vasopressin (AVP) and oxytocin (OT) were utilized to assess the specificity of neurohypophyseal hormone release after hemorrhage or infusion of hypertonic saline to trained conscious dogs. Phlebotomy of 12.5 and 25 ml/kg produced increases in plasma AVP from 1.0 +/- 0.2 to 7.8 +/- 2.1 and 41.6 +/- 9.7 (SEM) microunit/ml respectively, and both responses differed significantly from values in control experiments (P less than 0.01 after the first phlebotomy and P less than 0.001 after the second phlebotomy). Plasma OT concentrations rose from baseline values of 1.1 +/- 0.4 to 3.3 +/- 0.6 and 8.3 +/- 1.7 microunit/ml (P less than 0.005 and P less than 0.001 compared to controls); plasma osmolality and sodium concentrations were unchanged. Both log AVP and log OT were highly correlated with the quantity of blood removed (r = 0.92 and -0.82, each P less than 0.001). Infusion of hypertonic (20g/dl) NaCl (3.4 meq/kg) over 20 min caused plasma osmolality and sodium to rise from 304 +/- 1.0 mosm/kg and 143 +/- 3.0 meq/liter to 316 +/- 1.0 mosm/kg and 150 +/- 3.0 meq/liter (each P less than 0.001). Plasma AVP rose from 1.5 +/- 0.2 to 2.4 +/- 0.2 microunit/ml (P less than 0.0025) and OT rose from 1.2 +/- 0.5 to 2.6 +/- 0.7 microunit/ml (P less than 0.005). The stimulus response ratios (change in log hormone concentration divided by the rise in plasma osmolality) were comparable for both hormones (0.024 +/- 0.006 for AVP and 0.031 +/- 0.008 for OT; P less than 0.4). The data indicate that hemorrhage or hypertonic saline stimulate release of both AVP and OT. After hemorrhage, there is greater stimulation of AVP than OT, whereas there is comparable stimulation of both peptides after hypertonic saline.
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PMID:The effect of hemorrhage and hypertonic saline upon plasma oxytocin and arginine vasopressin in conscious dogs. 74 39

Rat posterior pituitaries were extracted in acid and total rat neurophysins were isolated. Preparative disc gel electrophoresis separated the total neurophysins into three main peptides of differing electrophoretic mobility. Antisera raised in rabbits recognized a common antigenic site in the three peptides and identical radioimmunoassay standard curves were obtained with each of the isolated rat neurophysins. A homologous rat neurophysin radioimmunoassay was utilized to measure neurophysin in samples of unextracted rat plasma. Basal neurophysin levels, 3.7 +/- 0.2 ng/ml (mean +/- SEM), did not differ in samples collected by decapitation, carotid artery cannulation, or tail vein bleeding. Water-loading caused a significant reduction in neurophysin, 2.8 +/- 0.1 ng/ml, while hypertonic saline and dehydration caused a significant elevation, 10.4 +/- 2.1 and 8.0 +/- 1.4 ng/ml, respectively. A step-wise decrease in blood volume caused a step-wise increase in plasma neurophysin concentrations which returned to baseline with reinfusion of the withdrawn blood. A second hemorrhage caused an even greater release of neurophysin indicating large neurophysin reserve in the pituitary. In periodic tail vein samples over 23 days of pregnancy a rise in plasma neurophysin was found from day 14 continuing to parturition with a peak value of greater than 13 ng/ml by day 21. Two days postpartum the value was 4.6 +/- 0.3 ng/ml. With this homologous assay, the basal levels of plasma neurophysin are lower and the stimulated values higher than with previously reported heterologous assays. Therefore, the relative change with physiologic maneuvers is distinctly increased.
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PMID:Isolation, radioimmunoassay and physiologic secretion of rat neurophysins. 84 27

Inactivation of prostaglandins in the placenta was studied using an assay for 15-hydroxy-prostaglandin dehydrogenase (PGDH). Forty-four patients with normal single pregnancies between 38 and 42 weeks gestation were studied. Placentae were obtained before the onset of labour in 9, after spontaneous labour in 18, and after oxytocin-induced labour in 17 cases, PGDH-activity ranged from 54 to 495 nanomoles PGF2alpha/g placenta/minute, with a mean +/- SEM of 207 +/- 18 nanomoles/g/minute. The results indicate that the PGDH content of the human placenta does not change markedly with the onset or during the process of labour. The length of either spontaneous or oxytocin-induced labour was not influenced by the PGDH content of the placenta.
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PMID:Prostaglandin dehydrogenase in the placenta before and after the onset of labour. 103 17

The purpose of this study was to determine whether normal morphological development occurs in pituitary corticotrophs deprived of products of the hypothalamic paraventricular nucleus (PVN), e.g. corticotropin releasing hormone and arginine vasopressin (AVP), after PVN lesions. In addition, we have attempted to ascertain if the neurophysin/AVP-positive fibers innervating the fetal sheep anterior pituitary are affected by PVN lesions. The experimental groups consisted of fetal sheep in which 1) hypothalamic PVN lesions were placed at 118-122 days gestation (dGA) and the fetuses subsequently harvested while still in utero at 157 dGA or more (PVNX; n = 5); 2) sham PVN lesions were placed at 118-122 dGA and subsequently harvested as newborn lambs immediately after birth at 146.5 +/- 0.9 (mean +/- SEM) dGA combined with two uninstrumented fetuses harvested at 144 dGA or more but not in labor (perinatal; n = 6); and 3) no instrumentation was placed, and the fetuses were harvested at 120 dGA (control; n = 4). Two ACTH-immunoreactive cell types were seen in the anterior pituitary: 1) fetal cells: large and variably stained, often columnar, occurring in clusters and arranged in palisades; and 2) adult cells: smaller, darkly staining, and angular, occurring singly or in small groups. Quantification of the distribution of the two ACTH cell types was performed by scanning sections from a one in six series from each pituitary and estimating the percent area of each section in the well that showed adult type staining only. The observer was blind to the treatment group assignment of the sections. The estimated percentages of the portion of the pituitaries of each group that contained adult-type cells only were as follows: PVNX, 42.8 +/- 10.0%; perinatal, 90.9 +/- 2.1%; and control, 3.7 +/- 1.1% (mean +/- SEM; P less than 0.05 for all comparisons). There were no qualitative differences between all groups in the appearance of neurophysin-positive fibers innervating the anterior pituitary. AVP staining was strong in the internal zone of the median eminence in all groups, but was absent in the external zone of PVNX fetuses only. The intermediate pituitary lobes stained darkly in all groups. We conclude that lesions of the PVN at 120 dGA delay development of fetal pituitary corticotrophs, but have no effect on the presence of neurophysin-positive nerve fibers in the anterior pituitary.
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PMID:Hypothalamic paraventricular nuclear lesions delay corticotroph maturation in the fetal sheep anterior pituitary. 132 50

Ovariectomized ewes were treated with progesterone and oestradiol to induce oestrus (day of expected oestrus = day 0) and with progesterone on days 1 to 12. The concentrations of endometrial oxytocin receptors and the 13,14-dihydro-15-keto prostaglandin F2 alpha (PGFM) response induced by oxytocin were measured on days 12, 14, 16 and 18 after the cessation of progesterone treatment on day 12, by a receptor binding assay and direct radioimmunoassay, respectively. During the period of treatment, the concentrations of plasma progesterone were high and remained above 2 ng ml-1 until day 13 when they dropped rapidly to less than 0.5 ng ml-1 by day 14. The concentrations of oxytocin receptors in endometrium of control ewes were high (820.7 +/- 91.7 (SEM) fmol mg-1 protein). Treatment with progesterone significantly (P < 0.01) reduced the concentrations of the receptors on days 12 and 14 (144.1 +/- 65.0 and 200.4 +/- 45.4 fmol mg-1 protein, respectively). The receptor concentrations then increased to relatively high values on day 16 (1021.4 +/- 216.6 fmol mg-1 protein) and remained high until day 18 (677.7 +/- 103.4 fmol mg-1 protein).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increase in concentration of uterine oxytocin receptors and decrease in response to 13,14-dihydro-15-keto prostaglandin F2 alpha in ewes after withdrawal of exogenous progesterone. 132 30

Oxytocin infusions were initiated on day 10 of the oestrous cycle in ewes, and luteal regression was induced by injection of 100 micrograms cloprostenol on day 12. Blood samples were collected at frequent intervals via an indwelling jugular vein cannula to measure concentrations of progesterone and luteinizing hormone (LH) during the luteal and follicular phases in saline (n = 6) and oxytocin (n = 5) infused animals. The oxytocin infusion maintained peripheral plasma concentrations of 53 +/- 3.2 pg oxytocin ml-1 (mean +/- SEM) compared with values of about 1 pg ml-1 during oestrus in control ewes. Oxytocin infusion had no effect on luteal phase progesterone concentrations, the timing of luteolysis, basal luteinizing hormone (LH) secretion, LH pulse frequency, or the timing or height of the LH surge. Treated ewes came into oestrus significantly earlier than controls (P < 0.05) but ovulated normally. Uterine samples collected 96 h after cloprostenol injection (approximately day 2 of the cycle) showed that oxytocin receptor concentrations were significantly higher in the endometrium in ewes that had been given a 5 day oxytocin infusion than in control animals (556 and 262 fmol mg-1 protein, respectively: geometric means from ANOVA, P < 0.001), whereas myometrial receptor concentrations were not affected (113 and 162 fmol mg-1 protein, respectively). We conclude that the previously reported delay in luteal development caused by oxytocin infusion (Wathes et al., 1991) is not due to the inhibition or delay of ovulation, but must instead occur via a direct influence on the developing corpus luteum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oxytocin infusion on secretion of progesterone and luteinizing hormone and the concentration of uterine oxytocin receptors during the periovulatory period in cloprostenol-treated ewes. 133 45

The central nervous system modulates cardiovascular function and fluid and electrolyte balance in part through the actions of vasoactive peptides/neurotransmitters. The presence of several vasoactive peptides and their receptors in the hypothalamus suggests a possible interaction at this site. One level at which vasoactive peptides such as arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) might interact is through the mutual regulation of production and secretion in the hypothalamus. To determine whether AVP modulates ANP gene expression and secretion, we cultured fetal rat diencephalic neurons in the presence of AVP. AVP induced a significant increase in ANP secretion in dose-related fashion (mean +/- SEM basal ANP, 87 +/- 4 pg/ml; maximal mean AVP-stimulated ANP, 146 +/- 6 pg/ml; P less than 0.05, by analysis of variance). Neither oxytocin nor the vasoactive neuropeptide angiotensin-II had any effect on ANP secretion. The stimulatory effect of AVP was significantly blocked by coincubation with a V1 receptor antagonist, but was unaffected by a V2 receptor antagonist. The immunoreactive ANP secreted in response to AVP was the major brain isoform, ANP-(103-126). Coincubation with a calcium channel antagonist, nifedipine, had no effect on AVP-induced ANP secretion, while ryanodine, an inhibitor of intracellular calcium mobilization, significantly reduced the stimulatory effect of AVP. AVP induced a dose-related, nearly 3-fold maximal increase in ANP mRNA expression at 4 h. Coincubation of the neurons with a V1 receptor antagonist also significantly attenuated the increased ANP gene expression induced by AVP. These results indicate that AVP acts directly through V1 receptors on cultured fetal rat diencephalic neurons to augment ANP gene expression and secretion of the peptide. The effects are probably related to AVP-stimulated mobilization of intracellular calcium and not the result of calcium influx into the cell. These studies provide the first evidence that AVP modulates ANP production from cultured neurons. In the central nervous system, these two vasoactive neuropeptides might interact in part through the regulation of ANP production by AVP.
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PMID:Arginine vasopressin stimulates atrial natriuretic peptide gene expression and secretion from rat diencephalic neurons. 138 Apr 42

This study examined the effects of progesterone and intrauterine injection of ovine conceptus secretory proteins (oCSP) on endometrial responsiveness to oxytocin. Twelve ewes were ovariectomized on day 4 of the cycle (oestrus = day 0) and assigned in a 2 x 2 factorial arrangement, to receive either 1.5 mg ovine serum proteins (SP) or oCSP containing 25 micrograms ovine trophoblast protein 1 (oTP-1) (by radioimmunoassay) in 1.5 mg total protein into each uterine horn, via catheters, twice a day on days 11, 12, 13 and 14. Ewes received 200 mg progesterone per day (i.m.) from day 4 to day 10 or 15. Oxytocin-induced prostaglandin F2 alpha was measured as 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) on days 11, 12, 13 and 14 in plasma from three integrated, 10 min (10 ml) blood samples (0-10, 10-20, 20-30 min) obtained after intravenous injection of 20 iu oxytocin, and in a pre-oxytocin (-10 to 0 min) sample collected via an indwelling jugular catheter. The pre-oxytocin samples were also assayed for progesterone. Oxytocin-induced turnover of inositol phosphate was determined in endometrium on day 15 after hysterectomy. In ewes receiving progesterone to day 10, plasma progesterone decreased from about 12 to 2 ng ml-1 (SEM +/- 2.6) during the treatment period (days 11-14), but remained high (12-20 +/- 2.6 ng ml-1) in ewes that received progesterone to day 15. Intrauterine injection of oCSP resulted in high basal concentrations of PGFM on days 12 and 13 compared with SP-treated ewes (P less than 0.01). Treatments with progesterone did not affect basal PGFM concentrations. Treatment with oCSP abolished oxytocin-induced endometrial secretion of prostaglandin only if progesterone was maintained to day 15 (P less than 0.01); in ewes receiving such treatment, oCSP inhibited (P less than 0.01), but SP did not inhibit, oxytocin-induced endometrial turnover of inositol phosphate (P less than 0.06), which was greater in ewes treated with progesterone to day 10 than in those treated to day 15 (P less than 0.05). Ewes that responded to oxytocin with increased PGFM exhibited increased oxytocin-stimulated turnover of inositol phosphate on day 15. These results indicate that the antiluteolytic action oTP-1 exerts on the endometrium requires progesterone and that this mechanism involves inhibition of oxytocin-stimulated turnover of inositol phosphate.
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PMID:Effects of ovine conceptus secretory proteins and progesterone on oxytocin-stimulated endometrial production of prostaglandin and turnover of inositol phosphate in ovariectomized ewes. 162 35


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