Oxytocin and vasopressin 1a receptor gene expression in the cycling or pregnant human uterus

Helmer, Hanns; Hackl, Tanja; Schneeberger, Christian; Knöfler, Martin; Behrens, Otto K.; Kaider, A.; Husslein, Peter

doi:10.1016/s0002-9378(98)70027-4

Cited by 54 publications

(34 citation statements)

References 22 publications

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“…There is a tendency for an increase in density of oxytocin and vasopressin V 1a receptors at the onset of labor preterm and at term. The importance of both the oxytocin and the vasopressin V 1a receptor in uterine activation is supported by the studies of gene expression for these receptors (24). Although the present study was not completed as planned, we observed a dose-dependent inhibition by SR 49059 of vasopressin-induced contractions, whereas no such effect was observed against oxytocin.…”

Section: Discussionsupporting

confidence: 47%

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women

Steinwall

Bossmar

Gaud

et al. 2004

Acta Obstet Gynecol Scand

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Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women.Steinwall, Margareta; Bossmar, Thomas; Gaud, Christine; Åkerlund, Mats Link to publication Citation for published version (APA): Steinwall, M., Bossmar, T., Gaud, C., & Åkerlund, M. (2004). Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women. Acta Obstetricia et Gynecologica Scandinavica, 83(1), 12-18. DOI: 10.1111/j.1600-0412.2004 General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from the public portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal Background. Compounds that block uterine oxytocin and vasopressin V 1a receptors have a therapeutic potential in preterm labor and primary dysmenorrhoea. The orally active vasopressin V 1a receptor antagonist, SR49059, inhibits the effect of vasopressin on human uterine activity in vivo, but the influence on the response to oxytocin is unknown.Methods. In a placebo-controlled, double-blind, parallel-group, four-dose comparison, the inhibitory effect of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in humans was investigated. Sixteen healthy female subjects, who had previously undergone sterilization with tubal ligation, participated in intrauterine pressure recordings at one of the first 3 days of bleeding of two menstrual cycles. Intravenous bolus injections of 10 pmol/kg body weight of vasopressin (Period 1) and of 50 pmol/kg body weight of oxytocin (Period 2) were given 1 h before and 1 , 2 and 4 h after oral administration of 0 (placebo), 25 , 75 or 200 mg of SR 49059. The area between the recording curve and zero level of intrauterine pressure (AUC) was calculated. Vital signs as well as urine and plasma safety parameters were measured. The plasma concentrations of oxytocin, vasopressin and the study drug were also estimated.Results. The plasma concentrations of SR 49059 appeared to be dose related, with mean maximal values of 62.0, 163.7 and 468.0 ng/ml in the 25, 75 and 200 mg dose groups, respectively, in Period 1 with vasopressin and 34.4, 116.7 and 418.0 ng/mL, respectively, in Period 2 with oxytocin. T max was observed at about 1 h. The cumulative AUC over 50 min after vasopressin injection per se was significantly higher than that after oxytocin in spite of a five times lower dose and lower plasma concentrations. Pretreatment by SR 49059 caused a dose-related reduction in AUCs for vasopressin, whereas no such effect was seen for oxytocin. With vasopressin as an agonist, a lower diastolic bl...

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Section: Discussionsupporting

confidence: 47%

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women

Steinwall

Bossmar

Gaud

et al. 2004

Acta Obstet Gynecol Scand

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“…Amplification of cDNA was performed using 1 AL RT product using published primers for oxytocin receptor 19 (sense primer 5V-ATGTGGAGCGTCTGGGATG; antisense primer 5V-CGATGGCTCAGGACAAAG) and for GAPDH as a control (sense primer 5V-TCCTGCACCAC-CAACTGCTTAGC; antisense primer 5V-AGGTCCAC-CACCCTGTTGCTGTA). PCR was carried out in a total volume of 50 AL [5 AL RT product, 4.5 AL 10Â PCR buffer (Roche), 0.9 AL 10 mmol/L dNTPs (Roche), 0.5 AL Taq polymerase (Roche) and 0.15 Amol/L concentration of primers, made up in H 2 O].…”

Section: Methodsmentioning

confidence: 99%

Myometrial microvascular endothelial cells express oxytocin receptor

Weston¹

2003

BJOG: An International Journal of Obstetrics and Gynaecology

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Objective 1. To establish whether microvascular endothelial cells from the human myometrium (MMECs) express oxytocin receptor, and to compare its expression levels relative to HUVECs. 2. To verify an upregulation of oxytocin receptor expression in MMECs as a result of vascular endothelial growth factor (VEGF), which had been found in a previous study. Design Laboratory scientific study. Setting University department.Population or Sample Myometrial biopsies from 12 hysterectomy specimens.Methods MMECs and HUVECs were established in vitro. Immunohistochemistry of in vitro cultures was performed to investigate protein expression of the oxytocin receptor. Semi-quantitative RT-PCR and Northern blots were performed to examine the presence and relative abundance of oxytocin receptor mRNA in MMECs and HUVECs, and in both cell types with and without VEGF. Total RNA from oxytocin acetate (100 nmol/L) and vehicle stimulated endothelial cell cultures was used to examine gene expression differences on a 10.5K cDNA microarray. Main outcome measures Oxytocin receptor mRNA and protein; gene expression analysis.Results Oxytocin receptor mRNA and protein was present in MMECs. The level of expression was the same as for the HUVECs, but much less than the pregnant myometrium. No effect on gene expression could be demonstrated by gene expression microarray following 10 hours of oxytocin stimulation. Twenty-four hours of VEGF stimulation did not significantly alter oxytocin receptor mRNA expression in MMECs or HUVECs. Conclusion The myometrial microvasculature expresses oxytocin receptor. This finding means that oxytocin may exert some of its effects on the myometrial microvasculature. No evidence could be found for a transcriptional effect of oxytocin stimulation in this study, but further work on the role of the myometrial vessel oxytocin receptor is needed.

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“…There is, however, little evidence for regulation of vasopressin (V 1a ) receptor protein (Bossmar et al 1994) or mRNA (Helmer et al 1999) during pregnancy or labour. Thus, it is more likely that the oxytocin receptor has a role in uterine activity given the gestational changes in expression.…”

Section: Oxytocin and Vasopressin V 1a Receptor Concentrationsmentioning

confidence: 99%

Oxytocin Antagonists: Clinical and Scientific Considerations

Thornton

Vatish

Slater

2001

Experimental Physiology

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Preterm delivery is the largest cause of perinatal mortality and morbidity, yet the treatment of preterm labour has not been demonstrated to improve outcome. The reasons are numerous and complex, but they include a failure to understand the mechanism(s) of preterm labour, the multitude of different causes, the difficulty in diagnosis and the problems of outcome measurement in clinical trials. Recently, an oxytocin antagonist (atosiban) has been introduced into clinical practice in Europe. Although it may be an effective tocolytic, a beneficial effect on perinatal outcome has not been demonstrated. Atosiban has an effect at both oxytocin and vasopressin (V1a) receptors, which (assuming efficacy) raises the question as to whether oxytocin or vasopressin V1a antagonism is required for tocolysis. This review examines the rationale for tocolysis in preterm labour, the evidence for administration of atosiban and the role for oxytocin, vasopressin and their receptors in the onset of labour.

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Oxytocin and vasopressin 1a receptor gene expression in the cycling or pregnant human uterus

Cited by 54 publications

References 22 publications

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women

Inhibitory effects of SR 49059 on oxytocin-and vasopressin-induced uterine contractions in non-pregnant women

Myometrial microvascular endothelial cells express oxytocin receptor

Oxytocin Antagonists: Clinical and Scientific Considerations

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