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Depletion of calcium stores contributes to progesterone-induced attenuation of calcium signaling of G protein-coupled receptors

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Abstract

Progesterone non-genomically attenuates the calcium signaling of the human oxytocin receptor and several other Gαq protein-coupled receptors. High progesterone concentrations are found in the endometrium during pregnancy opposing the responsiveness of the underlying myometrium to labor-inducing hormones. Here, we demonstrate that within minutes, progesterone inhibits oxytocin- and bradykinin-induced contractions of rat uteri, calcium responses induced by platelet-activating factor in the human endometrial cell line MFE-280, and oxytocin-induced calcium signals in PHM1-31 immortalized pregnant human myometrial cells. Using human embryonic kidney (HEK293) cells as model system, we analyzed the molecular mechanisms underlying these effects. Our data indicate that progesterone rapidly depletes intracellular calcium stores. The resulting desensitization of the cells might contribute to the quiescence of the uterus during pregnancy.

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Acknowledgments

We thank Dr. Barbara Sanborn (Colorado State University, USA) for providing the PHM1-31 cells. We thank Silvia Wienken and Anne Franz for excellent technical assistance and Dr. Rolf Postina (Institute of Pharmaceutics and Biochemistry, University of Mainz) for critically reading the manuscript. This work was supported by the BMBF (JP2003G, Germany, and WTZ project number CZE01/027).

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Authors and Affiliations

  1. Institute of Pharmaceutics and Biochemistry, University of Mainz, Becherweg 30, 55099, Mainz, Germany

    Katja Gehrig-Burger & Gerald Gimpl

  2. Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic (ASCR), Prague, Czech Republic

    Jirina Slaninova

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  1. Katja Gehrig-Burger
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  2. Jirina Slaninova
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  3. Gerald Gimpl
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Correspondence to Katja Gehrig-Burger.

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Gehrig-Burger, K., Slaninova, J. & Gimpl, G. Depletion of calcium stores contributes to progesterone-induced attenuation of calcium signaling of G protein-coupled receptors. Cell. Mol. Life Sci. 67, 2815–2824 (2010). https://doi.org/10.1007/s00018-010-0360-4

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  • DOI: https://doi.org/10.1007/s00018-010-0360-4

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