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

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.