title: Enhanced purinergic contractile responses and P2X1 receptor expression in detrusor muscle during cycles of hypoxia-glucopenia and reoxygenation.
abstract: 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% O2, 5% CO2 and the balance nitrogen. Hypoxia-glucopenia was induced by switching perfusion to Krebs solution without glucose, gassed with 95% nitrogen and 5% CO2. 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 P2X1 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 P2X1-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 P2X1 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.
authors: R. A. Elliott: University of Leicester, Cancer Studies and Molecular Medicine, Reproductive Sciences Section, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester LE2 7LX, UK. rae5@leicester.ac.uk.
authors: R A
authors: RA
authors: Elliott
authors: A
authors: A
authors: Tonnu
authors: N
authors: N
authors: Ghaffar
authors: A H
authors: AH
authors: Taylor
authors: D G
authors: DG
authors: Tincello
authors: R I
authors: RI
authors: Norman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D058920:Purinergic P2X Receptor Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058474:Receptors, Purinergic P2X1 / Q000378:metabolism*; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000502:physiology*
chemical_list: D058920:Purinergic P2X Receptor Antagonists; D058474:Receptors, Purinergic P2X1; D001285:Atropine; D000255:Adenosine Triphosphate; D005947:Glucose; D000109:Acetylcholine; D010100:Oxygen