Abstract
Adenosine 5′-triphosphate is known to function as a potent extracellular messenger, producing its effects via a distinct family of cell surface receptors. Different receptor subtypes have been shown to modulate different cellular functions such as proliferation, differentiation and apoptosis. We have investigated the functional expression and apoptotic action of the P2X7 receptor in human malignant melanoma tissue and cells. Incubation of cells with the potent P2X7 receptor agonist 2′–3′-O-(4-benzoyl-benzoyl) adenosine 5′-triphosphate leads to a decrease in cell number, which is dose-dependent and reversible by the antagonist 1-N,O-bis-[5-isoquinoline-sulfonyl]-N-methyl-L-tyrosyl)-4-phenyl-piperazine. Synthesis of the P2X7 receptor by these cells has been established by reverse transcriptase-polymerase chain reaction, immunohistochemistry, immunocytochemistry and cellular accumulation of the fluorescent DNA-binding dye YO-PRO-1. The P2X7 receptors have been shown to mediate apoptotic actions of extracellular nucleotides and represent a novel target for melanoma therapy.
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Acknowledgements
The P2X7 receptor antibody was a gift from Roche Palo Alto (Palo Alto, Calif., USA).
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This work was supported by a pump-priming grant from the Royal College of Surgeons of Edinburgh, a Research Fellowship from the Royal College of Surgeons of England and a Paton/Masser research award from the British Association of Plastic Surgeons.
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White, N., Butler, P.E.M. & Burnstock, G. Human melanomas express functional P2X7 receptors. Cell Tissue Res 321, 411–418 (2005). https://doi.org/10.1007/s00441-005-1149-x
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DOI: https://doi.org/10.1007/s00441-005-1149-x