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The regulation of ATP release from the urothelium by adenosine and transepithelial potential.

Dunning-Davies, BM, Fry, CH, Mansour, D and Ferguson, DR (2012) The regulation of ATP release from the urothelium by adenosine and transepithelial potential. BJU Int.

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What's known on the subject? and What does the study add? Stretch of the urothelium, as occurs during bladder filling, is associated with a release of ATP that is postulated to act as a sensory neurotransmitter. The regulation of ATP release is poorly understood and in particular if there is a feedback mechanism provided by ATP itself. Adenosine, a breakdown product of ATP, is a potent inhibitor of stretch-induced ATP release, acting through and A1 receptor; endogenous levels are about 0.6 µM. Data are consistent with ATP release relying on the rise of intracellular Ca2+. Transepithelial potential also controls ATP release, also acting via an A1 receptor-dependent pathway. OBJECTIVES: •  To test the hypothesis that distension-induced ATP release from the bladder urothelium is regulated by adenosine as well as changes to transurothelial potential (TEP). •  To examine the role of changes to intracellular [Ca(2+) ] in ATP release. MATERIALS AND METHODS: •  Rabbit urothelium/suburothelium membranes were used in an Ussing chamber system. Distension was induced by fluid removal from the chamber bathing the serosal (basolateral) membrane face. •  The TEP and short-circuit current were measured. ATP was measured in samples aspirated from the serosal chamber by a luciferin-luciferase assay. •  Intracellular [Ca(2+) ] was measured in isolated urothelial cells using the fluorochrome Fura-2. All experiments were performed at 37 °C. RESULTS: •  Distension-induced ATP release was decreased by adenosine (1-10 µm) and enhanced by adenosine deaminase and A1- (but not A2-) receptor antagonists. •  Distension-induced ATP release was reduced by 2-APB, nifedipine and capsazepine; capsaicin induced ATP release in the absence of distension. •  ATP and capsaicin, but not adenosine, generated intracellular Ca(2+) transients; adenosine did not affect the ATP-generated Ca(2+) transient. •  ATP release was dependent on a finite transepithelial potential. Changes to TEP, in the absence of distension, generated ATP release that was in turn reduced by adenosine. CONCLUSION: •  Adenosine exerts a powerful negative feedback control of ATP release from the urothelium via A1 receptor activation. •  Distension-induced ATP release may be mediated by a rise of the intracellular [Ca(2+) ]. •  Modulation of distension-induced ATP release by adenosine and TEP may have a common pathway.

Item Type: Article
Divisions : Surrey research (other units)
Authors : Dunning-Davies, BM, Fry, CH, Mansour, D and Ferguson, DR
Date : 9 August 2012
DOI : 10.1111/j.1464-410X.2012.11421.x
Depositing User : Symplectic Elements
Date Deposited : 28 Mar 2017 15:50
Last Modified : 24 Jan 2020 11:48

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