Intracellular signaling and phasic myometrial contractions.
This article reviews recently reported observations regarding the intracellular signal transduction mechanisms involved in the generation of phasic contractions occurring in myometrial tissue. The presence of cell surface receptors for classic uterotonic agonists (including oxytocin, norepinephrine, vasopressin, acetylcholine, and prostaglandins [PGs]) has been well described; all are seven-membrane-spanning, G protein-coupled receptors. Occupancy of these receptors, coupled through members of the Gq and/or Gi families of heterotrimeric G proteins, results in stimulation of the phospholipase C-beta (PLC-beta) isoforms. Nonclassic uterotonic agonists, such as growth factors and cytokines, also activate the phosphatidylinositol (PI)-signaling pathway, in this case through tyrosine kinase receptor-mediated activation of the phospholipase C-gamma (PLC-gamma) isoforms. Several recent reports have demonstrated that activation of the PI-signaling pathway in uterine myocytes results in the development of cytosolic calcium oscillation-like phenomena. These cytosolic calcium oscillations appear to arise from repetitive cycles of emptying and refill of the endoplasmic reticulum calcium stores along with the influx of extracellular calcium. Calcium release from the endoplasmic reticulum calcium stores appears to be mediated by the inositol trisphosphate-sensitive and the ryanodine-sensitive receptor/channels; isoforms for both the these receptor/channels have been shown to be expressed in myometrial tissue. In summary, receptor-mediated activation of the PI-signaling pathway and the generation of cytosolic calcium oscillations appear to produce intermittent calcium transients that result in the development and maintenance of phasic myometrial contractions.
Department of Obstetrics and Gynecology, University of Chicago, Illinois 60637, USA. mphillip@babies.bsd.uchicago.edu
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Phillippe
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Chien
D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D005260:Female; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007527:Isoenzymes / Q000378:metabolism; D010507:Periodicity; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism; D014590:Uterine Contraction
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007527:Isoenzymes; D018160:Receptors, Cytoplasmic and Nuclear; D019837:Ryanodine Receptor Calcium Release Channel; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase