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Enhanced purinergic contractile responses and P2X 1 receptor expression in detrusor muscle during cycles of hypoxia–glucopenia and reoxygenation
Author(s) -
Elliott R. A.,
Tonnu A.,
Ghaffar N.,
Taylor A. H.,
Tincello D. G.,
Norman R. I.
Publication year - 2013
Publication title -
experimental physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.925
H-Index - 101
eISSN - 1469-445X
pISSN - 0958-0670
DOI - 10.1113/expphysiol.2013.075010
Subject(s) - purinergic receptor , detrusor muscle , atropine , hypoxia (environmental) , medicine , stimulation , urinary bladder , endocrinology , anesthesia , pharmacology , receptor , chemistry , oxygen , organic chemistry
New findings• What is the central question of this study? Given that the bladder in 60% of patients with detrusor overactivity exhibits increased atropine‐resistant contractile responses to nerve stimulation and that high intravesicular pressure is associated with episodes of hypoxia–glucopenia and reperfusion, we asked whether cycles of hypoxia–glucopenia and reoxygenation increases purinergic signalling in the rat bladder in vitro . • What is the main finding and its importance? Four cycles of hypoxia–glucopenia and reoxygenation augmented atropine‐resistant contractile responses of rat detrusor muscle strips subjected to electrical field stimulation via increased purinoceptor P2X 1 expression and ATP release. Purinergic antagonists blocked this augmentation, suggesting a possible therapeutic role for purinergic antagonists in the treatment of detrusor overactivity.Bladders from patients with detrusor overactivity have an increased atropine‐resistant contractile response to nerve stimulation. The bladder has also been shown to be very susceptible to hypoxia–glucopenia and reperfusion injury, leading to the hypothesis that episodes of hypoxia–glucopenia and reoxygenation result in increased atropine‐resistant responses to nerve stimulation in the detrusor muscle. Detrusor muscle strips were suspended in a Perspex organ bath chamber of volume 0.2 ml perfused with Krebs solution at 37°C aerated with 21% O 2 , 5% CO 2 and the balance nitrogen. Hypoxia–glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO 2 . Atropine‐resistant contractile responses increased by 40.5 ± 7.3% after four cycles of hypoxia–glucopenia (10 min) and reoxygenation (1 h), whereas α,β‐methylene ATP‐resistant responses did not increase. Expression of P2X 1 receptors in the bladder was increased after hypoxia–glucopenia and reoxygenation cycling, and ATP release from stimulated bladder strips during cycling was also increased. Other P2X receptor‐mediated mechanisms may also be involved in the augmentation of bladder contraction during hypoxia–glucopenia and reoxygenation cycling, because a non‐specific P2X antagonist blocked most of the augmented response, whereas a P2X 1 ‐specific antagonist prevented only part of the augmentation of contractile response induced by hypoxia–glucopenia and reoxygenation. In conclusion, four cycles of hypoxia–glucopenia and reoxygenation increased the purinergic, but not the cholinergic, contractile responses to nerve stimulation. Increased P2X 1 receptor expression and ATP release may have contributed to the augmentation of contractile response induced by hypoxia–glucopenia and reoxygenation. Purinergic antagonists may, therefore, be a useful therapeutic option for the treatment of overactive bladder with increased purinergic‐mediated contractions.