P2X and P2Y purinergic receptors on human intestinal epithelial carcinoma cells: Effects of extracellular nucleotides on apoptosis and cell proliferation

Robson Coutinho-Silva, Lynn Stahl, Kwok Kuen Cheung, Nathalia Enes De Campos, Carolina De Oliveira Souza, David M. Ojeius, Geoffrey Burnstock

Research output: Journal article publicationJournal articleAcademic researchpeer-review

102 Citations (Scopus)


Extracellular nucleotides interact with purinergic receptors, which regulate ion transport in a variety of epithelia. With the use of two different human epithelial carcinoma cell lines (HCT8 and Caco-2), we have shown by RT-PCR that the cells express mRNA for P2X1, P2X3, P2X 4, P2X5, P2X6, P2X7, P2Y 1, P2Y2, P2Y4, P2Y6, P2Y 11, and P2Y12 receptors. Protein expression for P2Y 1 and P2Y2 receptors was also demonstrated immunohistochemically, and P2X receptor subtype protein was present in the following decreasing order: P2X4 > P2X7 > P2X 1 > P2X3 > P2X6 > P2X5 > > P2X2. The functional presence of P2X7, P2Y 1, P2Y2, and P2Y4 receptors was shown based on the effect of extracellular nucleotides on apoptosis or cell proliferation, and measurement of nucleotide-dependent calcium fluxes using a fluorometric imaging plate reader in the presence of different selective agonists and antagonists. ATP, at high concentrations, induced apoptosis through ligation of P2X 7 and P2Y1 receptors; conversely, ATP, at lower concentrations, and UTP stimulated proliferation, probably acting via P2Y 2 receptors. We therefore propose that stimulation or dysfunction of purinergic receptors may contribute at least partially to modulation of epithelial carcinoma cell proliferation and apoptosis.

Original languageEnglish
Pages (from-to)G1024-G1035
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number5 51-5
Publication statusPublished - May 2005
Externally publishedYes


  • Adenosine 5′-triphosphate
  • Purinergic receptors

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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