The Signaling Mechanism of Contraction Induced by ATP and UTP in Feline Esophageal Smooth Muscle Cells

  • Kwon, Tae Hoon (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Jung, Hyunwoo (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Cho, Eun Jeong (Department of Pharmacology, College of Pharmacy, Chung-Ang University) ;
  • Jeong, Ji Hoon (Department of Pharmacology, College of Medicine, Chung-Ang University) ;
  • Sohn, Uy Dong (Department of Pharmacology, College of Pharmacy, Chung-Ang University)
  • Received : 2014.12.30
  • Accepted : 2015.04.16
  • Published : 2015.07.31


P2 receptors are membrane-bound receptors for extracellular nucleotides such as ATP and UTP. P2 receptors have been classified as ligand-gated ion channels or P2X receptors and G protein-coupled P2Y receptors. Recently, purinergic signaling has begun to attract attention as a potential therapeutic target for a variety of diseases especially associated with gastroenterology. This study determined the ATP and UTP-induced receptor signaling mechanism in feline esophageal contraction. Contraction of dispersed feline esophageal smooth muscle cells was measured by scanning micrometry. Phosphorylation of $MLC_{20}$ was determined by western blot analysis. ATP and UTP elicited maximum esophageal contraction at 30 s and $10{\mu}M$ concentration. Contraction of dispersed cells treated with $10{\mu}M$ ATP was inhibited by nifedipine. However, contraction induced by $0.1{\mu}M$ ATP, $0.1{\mu}M$ UTP and $10{\mu}M$ UTP was decreased by U73122, chelerythrine, ML-9, PTX and $GDP{\beta}S$. Contraction induced by $0.1{\mu}M$ ATP and UTP was inhibited by $G{\alpha}i_3$ or $G{\alpha}q$ antibodies and by $PLC{\beta}_1$ or $PLC{\beta}_3$ antibodies. Phosphorylated $MLC_{20}$ was increased by ATP and UTP treatment. In conclusion, esophageal contraction induced by ATP and UTP was preferentially mediated by P2Y receptors coupled to $G{\alpha}i_3$ and $G{\alpha}q$ proteins, which activate $PLC{\beta}_1$ and $PLC{\beta}_3$. Subsequently, increased intracellular $Ca^{2+}$ and activated PKC triggered stimulation of MLC kinase and inhibition of MLC phosphatase. Finally, increased $pMLC_{20}$ generated esophageal contraction.


Supported by : National Research Foundation of Korea (NRF)


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