Current therapies that aim to prevent preterm birth by inhibiting premature uterine contractions have detrimental off-target side effects for both infant and mother and are not generally effective.
To discover new compounds that inhibit uterine muscle contractions – or that enhance contractions to induce labor and treat postpartum hemorrhage – Jennifer Herington, Ph.D., and colleagues developed and validated a high-throughput screening assay. The investigators used mouse uterine muscle cells loaded with a calcium-sensitive fluorescent probe to detect intracellular calcium release, the final common pathway in uterine muscle contractions.
They screened for inducers of calcium release and inhibitors of oxytocin-induced calcium release (oxytocin enhances contractions and induces labor). From a collection of 2,727 small molecules, they identified four inhibitors for further study and demonstrated that these compounds inhibited contractility of mouse uterine muscle.
The findings, reported in the journal PLOS ONE, show that high-throughput screening for calcium release in uterine muscle cells is a valuable approach for identifying new compounds to treat preterm labor or postpartum hemorrhage.
This project was supported by the National Institutes of Health (grants TR000445, TR000446, HD044741, HD081121).
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