Imperial College London
Alternate

DrVassoTerzidou

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Reader in Obstetrics and Gynaecology
 
 
 
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Contact

 

+44 (0)20 7594 2164v.terzidou

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kim:2017:10.1124/mol.116.106013,
author = {Kim, SH and Pohl, O and Chollet, A and Gotteland, J-P and Fairhurst, ADJ and Bennett, PR and Terzidou, V},
doi = {10.1124/mol.116.106013},
journal = {MOLECULAR PHARMACOLOGY},
pages = {403--415},
title = {Differential Effects of Oxytocin Receptor Antagonists, Atosiban and Nolasiban, on Oxytocin Receptor-Mediated Signaling in Human Amnion and Myometrium},
url = {http://dx.doi.org/10.1124/mol.116.106013},
volume = {91},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - One of the most established roles of oxytocin (OT) is in inducing uterine contractions and labor. Apart from inducing contractions, our recent studies showed that OT can also activate proinflammatory pathways in both human myometrial and amnion cells, which suggests that the proinflammatory role of OT should be taken into account when developing tocolytics targeting the OT/oxytocin receptor (OTR) system. The OTR antagonist, atosiban, is currently used therapeutically for the treatment of preterm labor. We previously showed that atosiban fails to inhibit the proinflammatory effects of OT in human amnion; atosiban alone activates nuclear factor-κB (NF-κB) and mitogen activated protein kinases, thus upregulating downstream prolabor genes. In contrast with our findings with atosiban, the presence of the orally active OTR antagonist, nolasiban, reduced the effect of OT on NF-κB and p38 kinase activation in both myometrial and amnion cells. Consistent with the activation of these inflammatory mediators, OT led to increases in the expression of cyclooxygenase-2 and phosphorylated cytosolic phospholipase A2, which was reflected in prostaglandin E2 synthesis. Inhibition of NF-κB activation by nolasiban also translated to suppression of downstream prolabor gene expression, such as cyclooxygenase-2, C-C motif chemokine ligand 2, interleukin-6, and interleukin-8. We also demonstrated that nolasiban treatment alone has no significant stimulatory effect on both the myometrium and amnion. In conclusion, our findings indicate that nolasiban possesses promising potential as a novel tocolytic agent for both acute and maintenance therapy, as it inhibits both myometrial contractions and the proinflammatory effects of OT without the biased agonist effects.
AU  - Kim,SH
AU  - Pohl,O
AU  - Chollet,A
AU  - Gotteland,J-P
AU  - Fairhurst,ADJ
AU  - Bennett,PR
AU  - Terzidou,V
DO  - 10.1124/mol.116.106013
EP  - 415
PY  - 2017///
SN  - 0026-895X
SP  - 403
TI  - Differential Effects of Oxytocin Receptor Antagonists, Atosiban and Nolasiban, on Oxytocin Receptor-Mediated Signaling in Human Amnion and Myometrium
T2  - MOLECULAR PHARMACOLOGY
UR  - http://dx.doi.org/10.1124/mol.116.106013
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000396213600014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/47867
VL  - 91
ER  -
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