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.
|Journal||American Journal of Physiology - Gastrointestinal and Liver Physiology|
|Issue number||5 51-5|
|Publication status||Published - May 2005|
- Adenosine 5′-triphosphate
- Purinergic receptors
ASJC Scopus subject areas
- Physiology (medical)