RhoA/Rho-kinase cascade is involved in oxytocin-induced rat uterine contraction

Endocrinology. 2002 Mar;143(3):920-9. doi: 10.1210/endo.143.3.8696.

Abstract

The RhoA/Rho-kinase cascade is involved in various cellular functions, including migration, proliferation, and smooth muscle contraction. We examined the potential role of this pathway in oxytocin-induced uterine contraction. The specific Rho-kinase inhibitor Y-27632 inhibited oxytocin-induced rat uterine contraction on d 21 of pregnancy in a concentration-dependent manner, whereas the extent of this inhibition was reduced in the nonpregnant uterus. Y-27632 had no effect on oxytocin-induced intracellular Ca(2+) mobilization in myometrial cells. Immunoblot analysis showed that oxytocin increased the level of myosin light chain phosphorylation, and this increase was attenuated by Y-27632. Oxytocin increased the phosphorylation of myosin-binding subunit of myosin phosphatase, one of the major substrates of Rho-kinase, and this increase was reduced by Y-27632. The expression of Rho-kinase protein was shown to increase in the uterus during pregnancy compared with the nonpregnant uterus, whereas the expression of RhoA protein remained at the same level during pregnancy. RT-PCR and Northern blot analysis showed that the expression of Rho-kinase was up-regulated at the transcriptional level during pregnancy. These results suggest that the RhoA/Rho-kinase pathway may have an important role in oxytocin-induced uterine contraction, and that up-regulation of Rho-kinase is involved in the mechanism underlying the increased contractility of the pregnant myometrium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology
  • Animals
  • Calcium / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Immunoblotting
  • In Vitro Techniques
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Isometric Contraction / drug effects
  • Myosin Light Chains / metabolism
  • Oxytocin / pharmacology*
  • Phosphorylation
  • Pregnancy
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Pyridines / pharmacology
  • Rats
  • Rats, Wistar
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Transcription, Genetic
  • Uterine Contraction / drug effects
  • Uterine Contraction / physiology*
  • Uterus / metabolism
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein / biosynthesis
  • rhoA GTP-Binding Protein / genetics
  • rhoA GTP-Binding Protein / physiology*

Substances

  • Amides
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Intracellular Signaling Peptides and Proteins
  • Myosin Light Chains
  • Pyridines
  • Y 27632
  • Oxytocin
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • rhoA GTP-Binding Protein
  • Calcium