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The regulation of ATP release from the urothelium by adenosine and transepithelial potential.
Dunning-Davies, Bryony M; Fry, Christopher H; Mansour, Dina; Ferguson, Douglas R.
Afiliação
  • Dunning-Davies BM; Department of Pharmacology, University of Cambridge, Cambridge, UK.
BJU Int ; 111(3): 505-13, 2013 Mar.
Article em En | MEDLINE | ID: mdl-22882496
UNLABELLED: 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 0.6µM. 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bexiga Urinária / Adenosina / Trifosfato de Adenosina / Urotélio Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Bexiga Urinária / Adenosina / Trifosfato de Adenosina / Urotélio Limite: Animals Idioma: En Ano de publicação: 2013 Tipo de documento: Article