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- W2022611241 abstract "G protein-coupled receptor kinase 6 (GRK6) is a kinase responsible for mediating desensitization of agonist-occupied G protein-coupled receptors (GPCR). Continuous oxytocin stimulation of the oxytocin receptor (OXTR), a GPCR, results in receptor desensitization and decreased uterine contractility that can manifest as dysfunctional labor and uterine atony. The objective of this study was to determine whether GRK6 mediates OXTR desensitization in vivo, and whether it is involved in the pathogenesis of dysfunctional labor. GRK6 knockout (GRK6KO) and wild type (WT) mice were time-mated and then underwent surgical implantation of a uterine telemetry pressure catheter that detects changes in uterine pressure during labor. The resulting labor tracings were analyzed and the area under the contraction curve and the frequency of uterine contractions calculated and compared between GRK6KO and WT mice. Labor tracings were available from five GRK6KO and five WT mice. GRK6KO mice had significantly fewer live births compared to WT mice (24% vs. 65%, p=0.003). GRK6KO mice exhibited significantly greater uterine contractility during the six hours in which delivery occurred, as measured by area under the contraction curve (135.4 ± 44.8 vs. 72.5 ± 16.9 mm Hg*hour, p=0.03), and greater median (IQR) uterine contraction frequency (7.3 [6.0, 11.6] vs. 6.6 [5.3, 7.3] contractions per hour, p<0.0001) compared to WT mice. There was no difference in the median gestational age at delivery (19.3 vs. 19.5 days), or mean pup or placental weights (116.7 vs. 118.9 g and 13.9 vs. 12.7 g, respectively) between the two genotypes. Mice lacking GRK6, a kinase that mediates OXTR desensitization, demonstrate an enhanced uterine contractile phenotype, generating both greater contraction force and frequency compared to WT mice. OXTR desensitization likely plays an important role in the contractile response during labor, and may be an important cause of abnormal labor." @default.
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- W2022611241 date "2014-01-01" @default.
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- W2022611241 title "748: Mice lacking G protein-coupled receptor kinase 6 (GRK6) exhibit an enhanced uterine contractile phenotype resulting in stillbirth" @default.
- W2022611241 doi "https://doi.org/10.1016/j.ajog.2013.10.781" @default.
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