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, P2X4, P2X5, P2X6, P2X7, P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, and P2Y12 receptors. Protein expression for P2Y1 and P2Y2 receptors was also demonstrated immunohistochemically, and P2X receptor subtype protein was present in the following decreasing order: P2X4 > P2X7 > P2X1 > P2X3 > P2X6 > P2X5 >> P2X2. The functional presence of P2X7, P2Y1, 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 P2X7 and P2Y1 receptors; conversely, ATP, at lower concentrations, and UTP stimulated proliferation, probably acting via P2Y2 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.
Coutinho-Silva
Robson
R
Autonomic Neuroscience Institute, Royal Free and University College Medical School, London, United Kingdom. rcsilva@biof.ufrj.br
Stahl
Lynn
L
Cheung
Kwok-Kuen
KK
de Campos
Nathalia Enes
NE
de Oliveira Souza
Carolina
C
Ojcius
David M
DM
Burnstock
Geoffrey
G
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology*; D009711:Nucleotides / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D013997:Time Factors; D015032:Zinc / Q000494:pharmacology
D009711:Nucleotides; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C017199:2',3'-dialdehyde ATP; D000255:Adenosine Triphosphate; D015032:Zinc; D002118:Calcium