Modulation of bladder function by luminal adenosine turnover and A1 receptor activation
| Autor: | Gerard Apodaca, James R. Roppolo, Heather Herrington, H. Sandeep Prakasam, Edwin K. Jackson |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Adenosine Physiology Urinary Bladder Biology Epithelium Rats Sprague-Dawley Adenosine A1 receptor Internal medicine Cystitis medicine Animals Cyclophosphamide Urinary bladder Receptor Adenosine A1 Articles Purinergic signalling Adenosine A3 receptor Adenosine receptor Rats medicine.anatomical_structure Endocrinology Models Animal Female Rabbits Bladder function medicine.drug |
| Zdroj: | American Journal of Physiology-Renal Physiology. 303:F279-F292 |
| ISSN: | 1522-1466 1931-857X |
| Popis: | The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), 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 A1 receptors with 2-chloro- N6-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 find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1 receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis. |
| Databáze: | OpenAIRE |
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