ATP and purinergic receptor–dependent membrane traffic in bladder umbrella cells

Wang, Edward C.Y.; Lee, Jey-Myung; Ruiz, Wily G.; Balestreire, Elena M.; Bodungen, Maximilian von; Barrick, Stacey; Cockayne, Debra A.; Birder, Lori A.; Apodaca, Gerard

doi:10.1172/jci24086

Cited by 208 publications

(243 citation statements)

References 69 publications

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“…ATP released from the urothelium or surrounding tissues may also regulate membrane trafficking in urothelial cells. This is supported by recent studies in the urinary bladder where urothelial-derived ATP release purportedly acts as a trigger for exocytosis-in part via autocrine activation of urothelial purinergic (P2X; P2Y) receptors (669). These findings suggest a mechanism whereby urothelial cells sense or respond to ATP and thereby translate extracellular stimuli into changes in afferent and urothelial function.…”

Section: Neuron-like Properties Of the Urothelium: Interaction With Asupporting

confidence: 64%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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This article summarizes anatomical, neurophysiological, pharmacological, and brain imaging studies in humans and animals that have provided insights into the neural circuitry and neurotransmitter mechanisms controlling the lower urinary tract. The functions of the lower urinary tract to store and periodically eliminate urine are regulated by a complex neural control system in the brain, spinal cord, and peripheral autonomic ganglia that coordinates the activity of smooth and striated muscles of the bladder and urethral outlet. The neural control of micturition is organized as a hierarchical system in which spinal storage mechanisms are in turn regulated by circuitry in the rostral brain stem that initiates reflex voiding. Input from the forebrain triggers voluntary voiding by modulating the brain stem circuitry. Many neural circuits controlling the lower urinary tract exhibit switch-like patterns of activity that turn on and off in an all-or-none manner. The major component of the micturition switching circuit is a spinobulbospinal parasympathetic reflex pathway that has essential connections in the periaqueductal gray and pontine micturition center. A computer model of this circuit that mimics the switching functions of the bladder and urethra at the onset of micturition is described. Micturition occurs involuntarily in infants and young children until the age of 3 to 5 years, after which it is regulated voluntarily. Diseases or injuries of the nervous system in adults can cause the re-emergence of involuntary micturition, leading to urinary incontinence. Neuroplasticity underlying these developmental and pathological changes in voiding function is discussed.

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Section: Neuron-like Properties Of the Urothelium: Interaction With Asupporting

confidence: 64%

Neural Control of the Lower Urinary Tract

2009

Encyclopedia of Neuroscience

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“…Moreover, both, ATP and adenosine have been extensively described to participate in bladder signaling [28,[49][50][51][52][53]. Urothelium is a source of ATP release [28,50,51] and it is also an important site of adenosine biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…Urothelium is a source of ATP release [28,50,51] and it is also an important site of adenosine biosynthesis. Importantly, both ATP and adenosine have functions in exocytosis of umbrella cell layer [52,53], which is the mechanism to increase the luminal surface area when the bladder fills (cytoplasmatic discoidal/fusiform vesicles fuse with the apical plasma membrane) [54]. The ATP released by urothelium is responsible for micturition reflex, through P2X3 from subepithelial nerve fibers [55].…”

Section: Discussionmentioning

confidence: 99%

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Rockenbach

Braganhol

Dietrich

et al. 2014

Purinergic Signalling

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According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5′-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5′-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5′-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5′-nucleotidase/ CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5′-nucleotidase/ CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

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“…This hypothesis is supported by a study published in 2005, which found that urothelial-derived ATP release in the urinary bladder purportedly acts as a trigger for exocytosis-in part via autocrine activation of urothelial purinergic (P2X and P2Y) receptors. 40 …”

Section: Role Of Different Receptors and Substances In Urothelial Funmentioning

confidence: 99%

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

2007

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SUMMARYAlthough the urinary bladder urothelium has classically been thought of as a passive barrier to ions and solutes, a number of novel properties have been recently attributed to urothelial cells. Studies have revealed that the urothelium is involved in sensory mechanisms (i.e. the ability to express a number of sensor molecules or respond to thermal, mechanical and chemical stimuli) and can release chemical mediators. Localization of afferent nerves next to the urothelium suggests that urothelial cells could be targets for neurotransmitters released from bladder nerves or that chemicals released by urothelial cells could alter afferent nerve excitability. Taken together, these and other findings highlighted in this article suggest a sensory function for the urothelium. Elucidation of mechanisms that influence urothelial function might provide insights into the pathology of bladder dysfunction.

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ATP and purinergic receptor–dependent membrane traffic in bladder umbrella cells

Cited by 208 publications

References 69 publications

Neural Control of the Lower Urinary Tract

Neural Control of the Lower Urinary Tract

NTPDase3 and ecto-5′-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression

Mechanisms of Disease: involvement of the urothelium in bladder dysfunction

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