<b>ATP release from bladder urothelium and serosa in a rat model of partial bladder outlet </b><b>obstruction </b>

Abstract

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.

Elevated hydrostatic pressure stimulates ATP release which mediates activation of the NLRP3 inflammasome via P2X4 in rat urothelial cells

“…If the inflammation-driven damage to the bladder reaches a state where fibrosis and nerve damage occur, symptoms can persist even after removal of the obstruction via surgical intervention [5–8]. A number of studies using animal models have demonstrated that pBOO results in upregulation of pro-inflammatory cytokines such as IL-1β and increased bladder weight [2, 9–11]. Based on these findings, we speculate that a link exists between pBOO-associated mechanical insults, such as elevated intravesical pressure, and inflammation of the bladder tissue; however, no study to date has ever examined a link between elevated pressure and activation of the inflammasome.…”

Urinary bladder organ hypertrophy is partially regulated by Akt1-mediated protein synthesis pathway

“…Studies in many experimental species including rats, mice, rabbits, and guinea pigs show that fibrosis and inflammation are common factors in urinary bladder hypertrophy (Metcalfe et al, 2010). The cues that lead to fibrosis and inflammation in the urinary bladder are not clear, but have been suggested to involve a number of processes including but not limit to up-regulation of transforming growth factor (TGF)-β1 (Jiang et al, 2015, Zhang and Qiao, 2012), imbalance between matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) (Yang et al, 2013), mast cell accumulation (Michishita et al, 2015), ATP release from serosa (Shiina et al, 2016), oxidative stress and free radical damage (Lin et al, 2011b), and up-regulation of nerve growth factor (NGF) and other growth factors (Chung et al, 2010, Steers and Tuttle, 2006, Zhang and Qiao, 2012). Many of these cues are related to activation of the serine/threonine kinase Akt that serves as a central stage in signal transduction.…”

New Frontiers in Molecular and Imaging Research on Evaluation and Diagnosis of Bladder Outlet Obstruction in Women

“…In a rat model, partial bladder outlet obstruction induced increased urothelial ATP release (47). In a prospective trial studying 79 male patients with BOO due to BPH and 22 asymptomatic controls, urinary ATP was significantly elevated in the BOO group, suggesting it could be used as a highly sensitive non-invasive biomarker of BOO (48).…”