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The effects of non-steroidal anti-inflammatory compounds on human myometrial contractility
Robert J Sawdy1, Mark H F Sullivan, Phillip R Bennett
1Department of Obstetrics & Gynaecology, Wolfson and Weston Centre for Family Health, Institute of Reproductive & Developmental Biology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
Objective:
To investigate the effects of inhibitors of COX-1 or COX-2 on myometrial prostaglandin synthesis and on spontaneous contractions in human myometrium.
Methods:
Cultured myometrial cells were incubated with SC 58560 (COX-1 selective inhibitor) or SC 58236 (COX-2 selective inhibitor), and the production of prostaglandins determined by ELISA. Spontaneously contracting strips of isolated gravid human lower segment myometrium were incubated with SC 58236, meloxicam, DFU, or nimesulide (COX-2 selective inhibitors), with SC 58560 (COX-1 selective inhibitor) or indomethacin (non-selective inhibitor).
Results:
SC 58236 inhibited the production of prostaglandins from myometrial cells, whereas SC 58560 had less effect. Nimesulide (100 microM) and indomethacin (300 microM) completely inhibited myometrial contractions, whereas meloxicam, DFU, SC 58236 and SC 58560 had less effect.
Conclusions:
There was no relationship between the inhibition of prostaglandin production and the effects of the compounds on contractility. Myometrial prostaglandin synthesis does not seem to be essential for spontaneous contractility.
Insights
Cyclooxygenase (COX) inhibitors affect prostaglandin synthesis in human myometrium. However, inhibiting prostaglandin production does not appear essential for myometrial contractility.
Area of Science:
- Biochemistry
- Reproductive Biology
- Pharmacology
Background:
- Prostaglandins play a role in uterine function.
- Cyclooxygenase (COX) enzymes are involved in prostaglandin synthesis.
- Understanding the role of COX-1 and COX-2 in myometrial activity is crucial for reproductive health.
Purpose of the Study:
- To investigate the impact of COX-1 and COX-2 inhibitors on prostaglandin synthesis in human myometrium.
- To determine the effect of these inhibitors on spontaneous myometrial contractions.
Main Methods:
- Myometrial cells were cultured and treated with selective COX-1 (SC 58560) or COX-2 (SC 58236) inhibitors.
- Prostaglandin production was quantified using ELISA.
- Isolated gravid human myometrium strips were incubated with various COX inhibitors (selective and non-selective) to assess contractility.
Main Results:
- SC 58236 significantly inhibited prostaglandin production in myometrial cells, while SC 58560 had a minimal effect.
- Non-selective COX inhibitor indomethacin and selective COX-2 inhibitor nimesulide (at high concentrations) completely abolished myometrial contractions.
- Other tested COX-2 inhibitors (meloxicam, DFU, SC 58236) and the COX-1 inhibitor SC 58560 showed limited effects on contractility.
Conclusions:
- No direct correlation was observed between the degree of prostaglandin synthesis inhibition and the impact on myometrial contractility.
- Myometrial prostaglandin synthesis is likely not a critical factor for spontaneous uterine contractions.