Oxytocin-induced desensitization of the oxytocin receptor.

OBJECTIVE

The purpose of this study was to characterize the oxytocin-induced desensitization of oxytocin-stimulated rises of intracellular calcium in cultured human myocytes.

STUDY

DESIGN

Culture lines were begun from biopsy specimens of myometrium that had been obtained from women who underwent low transverse cesarean deliveries. Fluorescence changes of calcium green-1 were used to demonstrate the rises of intracellular free calcium. Cells were exposed to 10 nmol/L oxytocin for 1 to 6 hours before the experimentation, allowed to rest for 10 minutes, and then tested for the fluorescence increases that resulted from exposure to 10 nmol/L oxytocin and micromol/L prostaglandin F(2)(alpha). Subpopulations were defined as type 1 (responded to both oxytocin and prostaglandin F(2)(alpha)), type 2 (responded only to oxytocin), type 3 (responded only to prostaglandin F(2)(alpha)), or type 4 (responded to neither). The distribution of the subpopulations of cells was assessed by the determination of the response of every cell in every experimental run.

RESULTS

Pretreatment with oxytocin resulted in a decrease in the percentage of cells that responded to subsequent oxytocin exposure. The decrease was dependent on the duration of oxytocin exposure and was well fit with the Boltzmann sigmoid function. The duration of oxytocin exposure that yielded half-inactivation was 4.2 hours. Without oxytocin pretreatment, the distribution of subpopulations were 37.0% +/- 18.0% (type 1), 23.1% +/- 11.5% (type 2), 12.6% +/- 8.0% (type 3), and 27.3% +/- 22.9% (type 4). After 6 hours of oxytocin pretreatment, the percentage of type 1 and type 2 cells decreased to 2.4% +/- 3.8% and 2.6% +/- 2.4%, respectively, although the percentage of type 3 and type 4 cells increased to 20.4% +/- 18.9% and 74.6% +/- 22.1%, respectively.

CONCLUSION

Oxytocin-induced desensitization of myocytes to oxytocin stimulation occurred over a clinically relevant time frame (4.2 hours). Continued responsiveness of the cells to prostaglandin F(2)(alpha) stimulation after 6 hours of oxytocin pretreatment indicated that postreceptor signaling pathways were maintained, which indicates that the oxytocin receptor likely is involved in the mechanism of myocyte desensitization to oxytocin stimulation.