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Extracellular ATP induces cytoplasmic and nuclear Ca2+ transients via P2Y2 receptor in human biliary epithelial

Christoph Elsing1, Tihomir Georgiev, Christian A Hübner

  • 1Department of Gastroenterology, St Elisabeth Hospital, Dorsten, Germany.

Anticancer Research
|September 21, 2012
PubMed

Insights

Extracellular adenosine triphosphate (ATP) activates P2Y2 and P2Y4 receptors in biliary cancer cells, influencing intracellular calcium. P2Y2 receptors are key targets for novel biliary cancer treatments.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Extracellular nucleotides, including adenosine triphosphate (ATP), are crucial for biliary epithelial cell function.
  • Nucleotide receptors represent promising therapeutic targets for epithelial cell dysfunction and cancer.

Purpose of the Study:

  • To investigate the expression and functional characteristics of nucleotide receptor subtypes in biliary epithelial cancer cells (Mz-Cha-1).
  • To determine the role of extracellular nucleotides in regulating intracellular and nuclear calcium signaling in these cells.

Main Methods:

  • Functional assays measuring intracellular Ca(2+) increase in response to various nucleotide agonists.
  • Analysis of purinergic receptor subtype mRNA and protein expression using RT-PCR and Western blotting.
  • Confocal imaging and nuclear staining to visualize calcium transients in cytosolic and nuclear compartments.

Main Results:

  • Extracellular ATP and uridine triphosphate (UTP) dose-dependently increased intracellular Ca(2+) in Mz-Cha-1 cells.
  • Functional expression of P2Y2 and P2Y4 purinoceptors was confirmed, with P2Y2 receptor protein expression identified by Western blot.
  • ATP induced significant cytosolic and nuclear Ca(2+) transients, suggesting a role in regulating nuclear function.

Conclusions:

  • Biliary epithelial cancer cells express specific P2Y receptor subtypes, notably P2Y2 and P2Y4.
  • P2Y2 receptors are functionally expressed and represent a potential therapeutic target for biliary cancer treatment strategies.

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