Aim: Succinate activates the receptor GPR91 identified in the bladder. The present study aims to unravel the mechanisms of bladder relaxation by succinate and how the receptor is involved in structural and functional changes of the bladder. Methods: Physiological recordings of bladder function were carried out by cystometry and organ bath from C57BL/6 mice, homozygous GPR91 −/− mice, and Sprague-Dawley (SD) rats. GPR91 expression was confirmed by polymerase chain reaction and tissue morphology was examined by light (Masson trichrome) and fluorescence microscopy. Nitric oxide (NO) and ATP secretion were measured. Results: Bladders of GPR91 KO mice had a greater mass to body weight ratio with a thicker bladder wall compared to C57BL/6 mice. They also displayed increased basal and maximal bladder pressures, and decreased intercontraction intervals, bladder capacity, micturition volume, and compliance. During cystometry, bladders of SD rats and C57BL/6 mice instilled with succinate (10 mM) showed signs of relaxation while bladders of GPR91 KO mice were unresponsive. Similarly, in organ bath, succinate relaxed bladder strips preincubated with carbachol, except GPR91 KO ones. Relaxation was stronger in the presence of urothelium and independent of NO synthesis. Bladder strips from all mice groups showed similar responses to KCl, carbachol, and electrical stimulation. In vitro, succinate increased NO secretion in urothelial cell culture of both C57BL6 and GPR91 KO mice while ATP secretion was potently decreased by succinate in C57BL6 culture only. Conclusion: Succinate through GPR91 is essential to bladder structure and contraction. GPR91 relaxes the detrusor partially by decreasing urothelial ATP secretion.

urine flow from internal vew of baldder neck. using by wireless capsule endoscopes (WCEs) for cystoscopy at voiding in vivo.METHODS: Experimental evaluation of capsule cystoscopy was performed in a 5-kg farm rabbits(n¼6). The capsule was inserted after incision of bladder. Images were continuously transmitted at a rate of four frames per second to a laptop computer and processed using proprietary software. Manipulation of the WCE within the bladder was performed using a set protocol. We measured the ability to deploy and manipulate the capsule within the bladder. Feasibility of capturing and retrieving images in real time was also assessed. We used air bubble(injection by syringe) and dye(intravenous administration of indigocarmine) as urine flow tracer.RESULTS: The WCE was efficiently deployed and manipulated within the bladder passively by manual. The entire bladder mucosa realtime image transmission and capture was visualized. The urine flow rotated clockwise from ventral to visceral at bladder neck during voiding. Fig.a): closed bladder neck before voiding, b)c) :air bubble rotated fom 12 to 3 at clock and d)sucked to internal urethra,no apparent of the air bubble. Fig(A) :the dye was visualized on closed bladder neck before voiding Fig(B) :when bladder neck begun to open, the dye visualized a vortex with rotation clockwise like crescent moom.CONCLUSIONS: By this device, urine flow could be visualized a vortex with rotation clockwise from ventral to visceral at the bladder neck mucosa during voiding.

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All experiments were performed with measurement of continuous cystometry under urethane anesthesia. 1. Fiberphotometry: Optical probe was inserted into the ACC of Thy1-GCaMP (Green fluorescent protein-calmodulin protein) transgenic mice with a GCaMP in the brain cortex, and neural activity of the ACC was measured. 2. Optogenetics: To investigated excitatory neuron, photostimulation was performed with inserting an optical probe into the ACC of wild type mice and Thy1-ChR2 mice expressing ChR2 in cortex V layer excitatory neurons.RESULTS: 1. Fiberphotometry: The neural activity of the ACC was linked to micturition pressure change. (Fig. 1) 2. Optogenetics: Photostimulation to the ACC in Thy1-ChR2 mice induced an increase of micturition pressure, which was not observed in wild type mice. (Fig. 2) CONCLUSIONS: Neural activity in the ACC related to micturition reflex. Particularly, activation of ACC excitatory neurons induced micturition. Thus, the ACC is one of the important regions to regulate micturition reflex.