Adaptation to partial urethral obstruction in healthy aging LOU rats and the role of nerve growth factor signaling pathway in the bladder.

Aim: Aging is associated with poor ability to adapt to stress and abnormal nerve growth factor (NGF) profile. Lower urinary tract symptoms frequently disturb the quality of life of the aging population with no optimal treatment for both genders. The aim of the study was to compare the bladder response to bladder outflow obstruction in young and old LOU rats, a model of healthy aging that does not develop insulin resistance, and its relation to proNGF/NGF imbalance.

Receptor GPR91 contributes to voiding function and detrusor relaxation mediated by succinate.

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.

Antagonism of proNGF or its receptor p75 reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction.

Aims/hypothesis: Although 80% of diabetic patients will suffer from voiding difficulties and urinary symptoms, defined as diabetic voiding dysfunction (DVD), therapeutic targets and treatment options are limited. We hypothesise that the blockade of the pro-nerve growth factor (NGF)/p75 neurotrophin receptor (p75) axis by an anti-proNGF monoclonal antibody or by a small molecule p75 antagonist (THX-B) can restore bladder remodelling (represented by bladder weight) in an animal model of DVD. Secondary outcomes of the study include improvements in bladder compliance, contractility and morphology, as well as in voiding behaviour, proNGF/NGF balance and TNF-α expression.

Beta-3 Adrenoceptor Signaling Pathways in Urothelial and Smooth Muscle Cells in the Presence of Succinate.

Succinate, an intermediate metabolite of the Krebs cycle, can alter the metabolomics response to certain drugs and controls an array of molecular responses in the urothelium through activation of its receptor, G-protein coupled receptor 91 (GPR91). Mirabegron, a 3-adrenergic receptor (3-AR) agonist used to treat overactive bladder syndrome (OAB), increases intracellular cAMP in the detrusor smooth muscle cells (SMC), leading to relaxation. We have previously shown that succinate inhibits forskolin-stimulated cAMP production in urothelium.

Succinate decreases bladder function in a rat model associated with metabolic syndrome.

Aims: Succinate and its receptor, GPR91, have been implicated in different aspects of metabolic syndrome. As GPR91 is expressed in the urinary bladder, the aim of this study is to show the effect of chronically increased succinate levels on bladder function.

Materials And Methods: Healthy Sprague-Dawley (SD) rats and hypertensive Dahl rats received an intraperitoneal injection of either saline or succinate (50 mg/kg) daily for a period of 4 weeks.

Bladder overdistension with polyuria in a hypertensive rat model.

Aims: Polyuria can lead to progressive chronic bladder overdistension. The impact of polyuria on the bladder has been extensively studied in settings of either diabetes or sucrose diuresis in animals. The goal of this study was to investigate the outcomes of polyuria in a hypertension setting.

Succinate, increased in metabolic syndrome, activates GPR91 receptor signaling in urothelial cells.

Metabolic syndrome is associated with overactive bladder syndrome (OAB) and increased circulating levels of succinate, an intermediate of the Krebs cycle. The urothelium is an essential regulator of bladder muscle contraction. This study aimed to determine if GPR91, the succinate receptor, is expressed and functional in the bladder.