Modulation of bladder function by luminal adenosine turnover and A1 receptor activation.

American Journal of Physiology. Renal Physiology
H Sandeep PrakasamGerard Apodaca

Abstract

The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A(1), A(2A), A(2B), and A(3)), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A(1) receptors with 2-chloro-N(6)-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we...Continue Reading

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Citations

Nov 23, 2013·Purinergic Signalling·Geoffrey Burnstock
Sep 10, 2013·Neurourology and Urodynamics·Takeya KittaNaoki Yoshimura
Oct 30, 2013·Neurourology and Urodynamics·Ann T Hanna-MitchellLori A Birder
Jul 29, 2016·American Journal of Physiology. Renal Physiology·Leonie DurninVioleta N Mutafova-Yambolieva
Nov 24, 2017·American Journal of Physiology. Cell Physiology·Luciana I GalloGerard Apodaca
Apr 4, 2019·Scientific Reports·Nicolas MontalbettiMarcelo D Carattino
Oct 2, 2015·American Journal of Physiology. Renal Physiology·Nicolas MontalbettiMarcelo D Carattino
Mar 20, 2020·Physiological Reviews·Marianela G DalghiGerard Apodaca

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