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Molecular Mechanisms Regulating the Effects of Oxytocin on Myometrial Intracellular Calcium

  • Barbara M. Sanborn
  • Kimberly Dodge
  • Monju Monga
  • Ansha Qian
  • Wei Wang
  • Caiping Yue
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 449)

Abstract

Oxytocin stimulates an increase in intracellular calcium in uterine myometrium by several mechanisms. Several lines of evidence indicate that the oxytocin receptor is functionally coupled to GTP-binding proteins of the Gαq/11 class which stimulate phospholipase C activity. The IP3 generated as a result of phospholipase C activation can trigger release of calcium from intracellular stores. The finding that the oxytocin-stimulated increase in intracellular calcium in myometrial cells is greater in the presence of extracellular calcium than that in its absence indicates that oxytocin also has effects on calcium entry. This action is nifedipine-insensitive but may involve indirect stimulation of calcium entry through release-operated channels.

An anti-Gαq/11 antibody inhibits both oxytocin-stimulated GTPase activity and phospholipase C activity in myometrial membranes. The stimulation by oxytocin of phosphoinositide turnover in COS cells transfected with a plasmid expressing the oxytocin receptor is enhanced by cotransfection of Gαq. Co-transfection of intracellular domains of the oxytocin receptor causes varying degrees of interference with oxytocin-stimulated phosphoinositide turnover. The data suggest that more than one intracellular domain is involved in oxytocin receptor/G-protein coupling.

Oxytocin receptor stimulation of phospholipase C is inhibited by cAMP. This occurs in myometrial cells and in COS cells transfected with a plasmid expressing the receptor. The inhibitory mechanism involves the action of protein kinase A and is probably targeted indirectly at the Gαq/11 /phospholipase C coupling step.

Keywords

Intracellular Domain Calcium Entry Intracellular Free Calcium Oxytocin Receptor Myometrial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Barbara M. Sanborn
    • 1
    • 2
  • Kimberly Dodge
    • 1
  • Monju Monga
    • 2
  • Ansha Qian
    • 1
  • Wei Wang
    • 1
  • Caiping Yue
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyUniversity of Texas Houston Medical SchoolHoustonUSA
  2. 2.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of Texas Houston Medical SchoolHoustonUSA

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