From urothelial signalling to experiencing a sensation related to the urinary bladder

Birder, Lori A.; Wyndaele, Jean Jacques

doi:10.1111/apha.12011

Cited by 16 publications

(8 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Processing of information from the luminal surface to underlying cells involves a wide array of proteins that can be activated during a normal micturition cycle with corresponding release of various mediators (including ATP) from the urothelium that, in turn, can reflexively trigger normal micturition (Birder and Wyndaele, 2013;Burnstock, 2014b;Vlaskovska et al, 2001). For example, loss of the mechanotransducer protein, β1-integrin, from the rat urothelium results in abnormal purinergic signaling and bladder overactivity (Kanasaki et al, 2013).…”

Section: Role Of Purinergic Signaling In the Regulation Of Afferent Amentioning

confidence: 99%

P2X3 receptors and sensitization of autonomic reflexes

Ford

Undem²,

Birder

et al. 2015

Autonomic Neuroscience

View full text Add to dashboard Cite

Section: Role Of Purinergic Signaling In the Regulation Of Afferent Amentioning

confidence: 99%

P2X3 receptors and sensitization of autonomic reflexes

Ford

Undem²,

Birder

et al. 2015

Autonomic Neuroscience

View full text Add to dashboard Cite

“…The introduction of urgency as a symptom of lower urinary tract dysfunction has impelled translational research to advance understanding of sensory functions of micturition pathways (Abrams et al, 2002;Birder and Wyndaele, 2013). Although the mechanisms of bladder sensation are not fully characterized, improved knowledge of its neurophysiology and pathophysiology has substantiated sensory pathways as central components of micturition and bladder disorders, and various afferent transmitter systems or receptors have been identified as putative targets for future drugs Drake et al, 2010;Gonzalez et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats

Mistretta

Russo

Castiglione

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

The transient receptor potential melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity is available. This study characterizes a new TRPM8-selective antagonist (DFL23448 [5-(2-ethyl-2H-tetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol-4-ol]) and evaluates it in cold-induced behavioral tests and tests on bladder function and experimental bladder overactivity in vivo in rats. DFL23448 displayed IC 50 values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold, but it had limited activity (IC 50 . 10 mM) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. In rats, DFL23448 administered intravenously or orally had a half-life of 37 minutes or 4.9 hours, respectively. DLF23448 (10 mg/kg i.v.) reduced icilininduced "wet dog-like" shakes in rats. Intravesical DFL23448 (10 mg/l), but not vehicle, increased micturition intervals, micturition volume, and bladder capacity. During bladder overactivity by intravesical prostaglandin E 2 (PGE 2 ), vehicle controls exhibited reductions in micturition intervals, micturition volumes, and bladder capacity by 37%-39%, whereas the same parameters only decreased by 12%-15% (P , 0.05-0.01 versus vehicle) in DFL23448-treated rats. In vehicle-treated rats, but not in DFL23448-treated rats, intravesical PGE 2 increased bladder pressures. Intravenous DFL23448 at 10 mg/kg, but not 1 mg/kg DFL23448 or vehicle, increased micturition intervals, micturition volumes, and bladder capacity. During bladder overactivity by intravesical PGE 2 , micturition intervals, micturition volumes, and bladder capacity decreased in vehicle-and 1 mg/kg DFL23448-treated rats, but not in 10 mg/kg DFL23448-treated rats. Bladder pressures increased less in rats treated with DFL23448 10 mg/kg than in vehicle-or 1 mg/kg DFL23448-treated rats. DFL23448 (10 mg/kg i.v.), but not vehicle, prevented cold stress-induced bladder overactivity. Our results support a role for bladder TRPM8-mediated signals in experimental bladder overactivity.

show abstract

“…The apical urothelial cells have specialized function that maintain bladder-blood impermeability [1] via expression of uroplakin plaques [2] and tight junction proteins [3]. Because the urothelium is theorized to have additional properties, such as urothelial-afferent signaling [4] and immune surveillance [5], the ability to dissect out individual cells from the multi-layered urothelium would represent an advance in the field of urothelial biology. Physiologic studies on bladder urothelial function (such as patch clamp electrophysiology and calcium microfluorimetry) have often utilized primary dissociated cell cultures which loses cellular specificity.…”

Section: Introductionmentioning

confidence: 99%

A method to study bladder urothelial cellular function in situ

Chai²

2014

Bladder

View full text Add to dashboard Cite

OBJECTIVE:The bladder urothelium is comprised of basal, intermediate, and apical urothelial cells. Ability to functionally study an individual urothelial cell while preserving its in situ location would represent an advance in bladder urothelial biology. MATERIALS AND METHODS:Mice were euthanized and cardiac perfused with phosphate-buffered saline. Bladders were then excised. Urothelial sheets were dissected off the lamina propria using forceps with a microscope (5 × magnification). Sheets were stained with H&E. In separate experiments, cell-attached electrophysiology was performed by placing urothelial sheets in Ringer's bath solution, with either basal or apical surface down. Using 40 × magnification, individual urothelial cells from different layers were identified. Potassium currents on these cells were measured in situ using single channel patch-clamp technique. RESULTS: CONCLUSIONS:A novel approach was developed in which individual urothelial cells within the multi-layered urothelium were identified and functionally studied in situ. Electrophysiologic characterization revealed different phenotype between the cells from different layers. Single cells from an identified layer can be harvested off the urothelium allowing for other studies. This technique allows investigators to study various cellular functions while preserving cellular location within the urothelium.

show abstract

From urothelial signalling to experiencing a sensation related to the urinary bladder

Cited by 16 publications

References 48 publications

P2X3 receptors and sensitization of autonomic reflexes

P2X3 receptors and sensitization of autonomic reflexes

DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats

A method to study bladder urothelial cellular function in situ

Contact Info

Product

Resources

About