Augmented stretch activated adenosine triphosphate release from bladder uroepithelial cells in patients with interstitial cystitis.
OBJECTIVE
Extracellular adenosine triphosphate (ATP) has been shown to mediate inflammation and nociception and, therefore, it may have a role in symptoms associated with interstitial cystitis. We theorized that the bladder uroepithelium releases ATP in response to stretch and, furthermore, this process is augmented in interstitial cystitis.


METHODS
We quantitated ATP using the luciferin-luciferase assay. Urinary ATP levels were compared in 35 patients with interstitial cystitis and in 33 normal controls after pH correction. Cultured interstitial cystitis and normal urothelial cells from the bladder biopsies of 5 patients each were stretched with the Flexcell 2000 machine (Flexcell International Corp., McKeesport, Pennsylvania) and supernatant ATP concentrations were measured.


RESULTS
Mean urinary ATP plus or minus standard error of mean was significantly higher in patients with interstitial cystitis than in controls (L value 985 +/- 161 versus 377 +/- 27, p = 0.0007). Supernatant ATP released by stretched interstitial cystitis cells was stretch intensity dependent when comparing 0%, 10% and 20% elongation, and was also significantly higher in stretched interstitial cystitis than in stretched normal cells.


CONCLUSIONS
Adenosine triphosphate was significantly elevated in the urine of individuals with interstitial cystitis and the stretch activated release of ATP was augmented in interstitial cystitis urothelium. Increased extracellular ATP may have a role in mechanosensory transduction and to our knowledge it represents a novel hypothesis.
Sun
Y
Y
Division of Urology, Department of Surgery, Veterans Administration Maryland Health Care System, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Keay
S
S
De Deyne
P G
PG
Chai
T C
TC
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000652:urine; D002452:Cell Count; D002478:Cells, Cultured; D018856:Cystitis, Interstitial / Q000503:physiopathology*; D004847:Epithelial Cells / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology*; D014563:Urodynamics
D007633:Keratins; D000255:Adenosine Triphosphate