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Purinergic receptor‐mediated effects of adenosine 5′‐triphosphate in urological malignant diseases
Author(s) -
Shabbir Majid,
Burnstock Geoffrey
Publication year - 2009
Publication title -
international journal of urology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.172
H-Index - 67
eISSN - 1442-2042
pISSN - 0919-8172
DOI - 10.1111/j.1442-2042.2008.02207.x
Subject(s) - purinergic receptor , medicine , purinergic signalling , receptor , adenosine triphosphate , adenosine , cancer research , p2 receptor , adenosine receptor , prostate cancer , cancer , pharmacology , agonist
Adenosine 5′‐triphosphate (ATP) mediates a variety of biological functions and has been shown to play a physiological role in almost every system in the body. In the genito‐urinary system, extracellular ATP has been shown to play a functional role in several different capacities, ranging from nociception in the ureter and bladder, to erectile dysfunction via its action on different ‘purinergic receptors’. Discovery of the trophic effects of ATP has led to a surge in interest in this signalling system in various malignancies. To date five P2 receptor subtypes have been implicated in the growth inhibition of cancer cells, namely P2X 5 , P2X 7 , P2Y 1 , P2Y 2 and P2Y 11 . Limited data are available on urological malignancies. ATP induces its anti‐neoplastic effect primarily via purinergic receptor‐mediated apoptosis via calcium‐independent pathways, and this has been confirmed in vitro and in vivo . Studies have highlighted functional roles for the P2X 5 and/or P2Y 11 receptors in both hormone refractory prostate cancer and high‐grade bladder cancer, although the contributory effect of pro‐apoptotic P2X 7 receptors remains unclear. Clinical trials have shown intravenous ATP successfully attenuates a range of systemic symptoms associated with advanced malignancies. This raises the possibility that selective targeting of specific aberrant pathways may allow for treatment of advanced primary malignancies and their systemic effects.