BERKELEY, CA (UroToday.com) - Bladder urothelial cells (BUC) may play a key pathophysiologic role leading to PBS/IC. Epithelial cells lining hollow organs, including the bladder, may have neurosensory-like functions, as the cells can release adenosine triphosphate (ATP) in response to stretch. The bladder urothelial cells in PBS/IC patients show a more pronounced ATP release than do controls. Increased ATP release may result in increased P2X3 expression on the BUC, suggesting an autocrine role for ATP via this receptor.

Sun and Chai tested the theory that augmented purinergic mechanisms in BUC could help to explain hypersensory dysfunction in PBS/IC by looking at monolayers of cultured bladder urothelial cells derived from bladder biopsies of PBS/IC patients and comparing them to controls. They reported augmented extracellular ATP signaling after exposing the cells to low and high concentrations of ATP stimulation when compared to the control cells. When PBS/IC bladder urothelial cells were pretreated with suramin, a non-specific P2 antagonist, the amount of ATP released was significantly reduced. A similar finding occurred after treatment with heparin binding epidermal growth factor-like growth factor, which has been shown to be decreased in PBS/IC urine specimens.

Thus, purinergic activity, as manifested by extracellular ATP signaling, is significantly augmented in PBS/IC bladder urothelial cells, and treatments designed to block this activity might conceivably diminish the hypersensitivity that is the hallmark of the disease.

American Journal of Physiology Cell Physiology; 2005 in press, epublication August 17, 2005 ajpcell.00552.2004