Effect of oxytocin antagonists on the activation of human myometrium in vitro: atosiban prevents oxytocin-induced desensitization.
OBJECTIVE
Our purpose was to investigate whether the sensitivity of myometrial cells to oxytocin is affected by prolonged exposure to oxytocin antagonists.


METHODS
Tissue slices or cultured myometrial cells were exposed to peptides in vitro. Myometrial activation was studied by measuring the formation of inositol phosphates and the changes in intracellular calcium. Oxytocin binding was measured by saturation analysis.


RESULTS
Atosiban and related peptides inhibited oxytocin-induced myometrial activation as pure antagonists (inhibition constant 10 nmol/L) but had no effect on prostaglandin E2-induced activation. Long-term (> or = 24 hours) exposure to atosiban had no residual effect on oxytocin sensitivity. However, long-term exposure to oxytocin resulted in homologous desensitization and loss of oxytocin receptors. Oxytocin-induced desensitization was prevented by coincubation with atosiban.


CONCLUSIONS
Atosiban is a pure oxytocin antagonist and has a specific, reversible effect on myometrial cells in vitro. Its potential use for the management or even prevention of idiopathic preterm labor or to reverse uterine hypertony during oxytocin-induced labor should be tested in controlled clinical trials.
Phaneuf
S
S
Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, United Kingdom.
Asbóth
G
G
MacKenzie
I Z
IZ
Melin
P
P
López Bernal
A
A
D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D005260:Female; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D007425:Intracellular Membranes / Q000378:metabolism; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D010121:Oxytocin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
D007295:Inositol Phosphates; C047046:atosiban; D010121:Oxytocin; D002118:Calcium; D014668:Vasotocin