PubMed1992
OBJECTIVE: We wished to investigate the role of cAMP in the synergistic effect of corticotrophin-releasing factor and oxytocin on human myometrial contractility. DESIGN: Isolated human gestational myometrium obtained from Caesarean sections at term was studied in vitro. Static incubation techniques as well as tension recordings were applied to the tissue obtained. PATIENTS: The subjects were healthy pregnant women undergoing lower segment Caesarean section at term, prior to labour. MEASUREMENTS: Specimens obtained were immediately dissected into small strips and either incubated in multi-well trays (strip weight 2.75 mg) or superfused and used for tension recordings (strip weight 2.00 mg). cAMP accumulation was measured after incubation with oxytocin (0.1-10 nM), corticotrophin-releasing factor (1 nM) or a combination of both peptides. Tension generated by the muscle strips was recorded isometrically and response to oxytocin (0.01-10 nM), corticotrophin-releasing factor (1 nM) and forskolin (10 nM) expressed in force per gram wet tissue (N/g). RESULTS: Oxytocin (0.1 nM) causes a statistically significant dose-related decrease in cAMP when combined with 1 nM corticotrophin-releasing factor (P less than 0.001), as compared with cAMP stimulation by corticotrophin-releasing factor alone. Time course studies suggest a maximal effect at 1 minute. The hypothesis that an intracellular reduction of cAMP is a prerequisite for the synergistic response in contraction force was tested with tension recordings. Prevention of a decrease in cAMP in the tissue by addition of 10 nM forskolin to the superfusate abolished the potentiation between oxytocin and corticotrophin-releasing factor. CONCLUSIONS: These results indicate that a fall in cAMP concentration plays a vital mediating role in the synergistic interaction between oxytocin and corticotrophin-releasing factor.