Internalization and desensitization of the oxytocin receptor is inhibited by dynamin and clathrin mutants in human embryonic kidney 293 cells
Smith MP, Ayad VJ, Mundell SJ, McArdle CA, Kelly E, López Bernal A
Mol Endocrinol. 2006 Feb;20(2):379-88
During labour, the brain releases pulses of the hormone oxytocin to promote the contraction of muscles in the uterus and enable delivery of the baby. The role of oxytocin during labour has long been known and this hormone is often given to women to initiate or enhance contractions. However, the responses of women to oxytocin vary and studies have shown that with prolonged exposure, muscle cells become desensitized and less responsive to the hormone in order to protect against hypersensitivity.
Oxytocin achieves its effects by binding to receptors on the surfaces of muscle cells. It is believed that desensitization occurs due to the loss of these receptors and it is thought that this is mediated by a range of proteins, including the enzymes, G protein-receptor kinase (GRK) and dynamin, and the scaffolding protein, ß-arrestin. However, the precise roles of such proteins in the desensitization of uterine muscle cells are not fully understood. In this study, the researchers investigated the fate of oxytocin receptors in uterine muscle cells exposed to oxytocin and the roles of GRK, dynamin, ß-arrestin and other proteins in this process in laboratory-based experiments.
The researchers showed that oxytocin receptors became internalized and accumulated within cells exposed to oxytocin. In contrast, receptors remained on the surface membranes of control cells not exposed to the hormone. Internalization occurred rapidly and was dependent on both the concentration of oxytocin and the duration of exposure. Certain forms of the hormone vasopressin – which can also bind to the oxytocin receptor – also induced internalization, while other agents blocked the process. The experiments also revealed that GRK, dynamin and ß-arrestin are crucial for the internalization of the oxytocin receptor. They postulated that internalization of the receptor is a key factor in desensitization to oxytocin.
Further study of oxytocin receptor internalization and desensitization to the hormone is important to determine the relevance of this process during normal and premature births. It is hoped that such findings will improve our understanding of the processes occurring during labour and offer clinical benefits to women receiving oxytocin during childbirth.
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