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

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 horm...

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Bibliographic Details
Published in:Cellular and molecular life sciences : CMLS 2010-08, Vol.67 (16), p.2815-2824
Main Authors: Gehrig-Burger, Katja, Slaninova, Jirina, Gimpl, Gerald
Format: Article
Language:English
Subjects:
Animals
Biochemistry
Biomedical and Life Sciences
Biomedicine
bradykinin
Calcium
Calcium - metabolism
Cell Biology
Cell Line
Cellular biology
Endometrium - drug effects
Endometrium - physiology
endoplasmic reticulum
Estradiol - pharmacology
Estrus
Ethanol - pharmacology
Female
G protein-coupled receptor (GPCR)
Hormones
Humans
Kidney - drug effects
Kidney - physiology
Life Sciences
Molecular biology
Nifedipine - pharmacology
Non-genomic effect
oxytocin
Oxytocin - pharmacology
Pregnancy
Progesterone
Progesterone - metabolism
Progesterone - pharmacology
Rats
Rats, Wistar
Receptors, G-Protein-Coupled - drug effects
Receptors, G-Protein-Coupled - physiology
Research Article
Signal transduction
Signal Transduction - drug effects
uterus
Uterus - drug effects
Uterus - physiology
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Summary: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.
ISSN:1420-682X
1420-9071
DOI:10.1007/s00018-010-0360-4