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

作者：Dunning Davies Bryony M; Fry Christopher H^*; Mansour Dina; Ferguson Douglas R

来源：BJU International, 2013, 111(3): 505-513.

DOI：10.1111/j.1464-410X.2012.11421.x

• urothelium
• distension
• ATP release
• adenosine
• transepithelial potential

Objectives %26lt;br%26gt;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). %26lt;br%26gt;To examine the role of changes to intracellular [Ca2+] in ATP release. %26lt;br%26gt;Materials and Methods %26lt;br%26gt;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. %26lt;br%26gt;The TEP and short-circuit current were measured. ATP was measured in samples aspirated from the serosal chamber by a luciferin-luciferase assay. %26lt;br%26gt;Intracellular [Ca2+] was measured in isolated urothelial cells using the fluorochrome Fura-2. All experiments were performed at 37 degrees C. %26lt;br%26gt;Results %26lt;br%26gt;Distension-induced ATP release was decreased by adenosine (1-10 mu M) and enhanced by adenosine deaminase and A1- (but not A2-) receptor antagonists. %26lt;br%26gt;Distension-induced ATP release was reduced by 2-APB, nifedipine and capsazepine; capsaicin induced ATP release in the absence of distension. %26lt;br%26gt;ATP and capsaicin, but not adenosine, generated intracellular Ca2+ transients; adenosine did not affect the ATP-generated Ca2+ transient. %26lt;br%26gt;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. %26lt;br%26gt;Conclusion %26lt;br%26gt;Adenosine exerts a powerful negative feedback control of ATP release from the urothelium via A1 receptor activation. %26lt;br%26gt;Distension-induced ATP release may be mediated by a rise of the intracellular [Ca2+]. %26lt;br%26gt;Modulation of distension-induced ATP release by adenosine and TEP may have a common pathway.

• 出版日期2013-3