The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via G(alphai) signalling.

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Kim SH, MacIntyre DA, Hanyaloglu AC, Blanks AM, Thornton S, Bennett PR, Terzidou V

The oxytocin receptor antagonist, Atosiban, activates pro-inflammatory pathways in human amnion via G(alphai) signalling.

Mol Cell Endocrinol. 2016 Jan 15;420:11-23. doi: 10.1016/j.mce.2015.11.012. Epub 2015 Nov 14.

PubMed ID

26586210 [ View in PubMed

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Abstract

Oxytocin (OT) plays an important role in the onset of human labour by stimulating uterine contractions and promoting prostaglandin/inflammatory cytokine synthesis in amnion via oxytocin receptor (OTR) coupling. The OTR-antagonist, Atosiban, is widely used as a tocolytic for the management of acute preterm labour. We found that in primary human amniocytes, Atosiban (10 muM) signals via PTX-sensitive Galphai to activate transcription factor NF-kappaB p65, ERK1/2, and p38 which subsequently drives upregulation of the prostaglandin synthesis enzymes, COX-2 and phospho-cPLA2 and excretion of prostaglandins (PGE2) (n = 6; p < 0.05, ANOVA). Moreover, Atosiban treatment increased expression and excretion of the inflammatory cytokines, IL-6 and CCL5. We also showed that OT-simulated activation of NF-kappaB, ERK1/2, and p38 and subsequent prostaglandin and inflammatory cytokine synthesis is via Galphai-2 and Galphai-3 but not Galphaq, and is not inhibited by Atosiban. Activation or exacerbation of inflammation is not a desirable effect of tocolytics. Therefore therapeutic modulation of the OT/OTR system for clinical management of term/preterm labour should consider the effects of differential G-protein coupling of the OTR and the role of OT or selective OTR agonists/antagonists in activating proinflammatory pathways.

DrugBank Data that Cites this Article

Drugs

Atosiban

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Atosiban	Oxytocin receptor	Protein	Humans	Yes	Antagonist	Details