Search

INTRODUCTION AND OBJECTIVE:It is reported that the bladder functions are under the regulation of clock genes, which regulate circadian rhythm in organisms, and dysregulation of circadian bladder fu...

INTRODUCTION AND OBJECTIVES:The objective of this study was to evaluate the influence of ingested L-citrulline and L-arginine on the progression of bladder dysfunction in rats with chronic pelvic i...

positively associated with MMP-2 (p1⁄40.0074) and MMP-9/NGAL (p

INTRODUCTION AND OBJECTIVES: ATP from urothelium plays an essential role for afferent nerve stimulation via activation of P2X receptors in suburothelial afferent nerve plexus. However, molecular mechanisms and pathways of ATP release are largely unknown. We confirmed VNUT (Vesicular Nucleotide Transporter; PNAS 2008), plays an important role in vesicular storage of ATP in ATP-secreting cells, localized in Human and Mouse bladder urothelium. Here we have investigated the relationship between VNUT and Human clinical symptoms and urodynamic parameters, and the function of VNUT in mouse urothelial cells upon stretch stimulation. METHODS: Human bladder specimen (15 male patients) and C57BL mice were used. (1) RT-PCR (2) Immunostaining;using an anti-VNUT antibody in bladder specimen and primary culture cells. (3) Visualization of the real-time dynamics of ATP containing vesicles like exocytosis. (4) Photon imaging of ATP release;counting released ATP from control siRNA and VNUT siRNA treated urothelial cells upon mechanical stretch stimulation. (5) Comparison examination between symptomatic/urodynamic parameters and mRNA expression of VNUT in human urothelium. RESULTS: VNUT was highly expressed in the epithelium of human (fig.1) and mouse bladder tissue and primary urothelial cell culture. We also visualized the ATP-vesicles and their real-time exocytosis. Knockdown of VNUT in primary culture cells markedly reduced ATP release upon mechanical stretch stimulation (fig.2). VNUT RNA expression was negative correlation with FDV (First Desire to Void) (fig.3). CONCLUSIONS: VNUT plays an important role in stretch-elicited ATP release from urothelium. These findings suggest that urothelium should transmit ATP to afferent neurons by a mechanism of exocytosis. Source of Funding: Grant-in-Aid for Scientific Research, Grant-in-Aid for Young Scientists(B) from JSPS

creased at 1 week and remained doubled at 4 weeks during continuous CMG. This was paralleled by similar increases in bladder compliance. A striking reduction (50%) in EUS EMG activity during filling was also seen with PNC. Isovolumetric CMG in the PNC groups revealed a 40% reduction in peak bladder contraction pressures over baseline and a 30% reduction in isovolumetric bladder contraction areas under the curves. CONCLUSIONS: In this preliminary study, we have shown that bilateral pelvic nerve crush in the rat is a promising, long-lasting model of UAB, demonstrating both bladder and outlet dysfunction consistent with pelvic nerve denervation. Increased ICI, bladder compliance, and decreased EUS activity are consistent with decreased afferent sensitivity with PNC. Decreased bladder contraction strength is consistent with compromised efferent function. By establishing a chronic rat model for UAB in otherwise normal animals, we can test potential therapies for treating UAB and voiding dysfunction, thereby addressing both afferent and efferent dysfunction.