Is electrolyte transfer across the urothelium important?: ICI‐RS 2015

McCloskey, Karen; Vahabi, Bahareh; Fry, Christopher

doi:10.1002/nau.23085

Cited by 4 publications

(5 citation statements)

References 42 publications

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“…Among them were umbrella cells, which build up the luminal lining in the proximal parts of the urethra being covered with an urothelium and which can be readily identified by virtue of their position and morphology. This is in line with the previously reported ENaCα-immunoreactivity at the luminal membrane of umbrella cells in the rat urinary bladder (Smith et al, 1998 ) and functional investigation of this cell type (McCloskey et al, 2017 ). Notably, this cell layer did not consistently express tdTomato with positive and negative umbrella cells occurring in a mosaic pattern (Figure 3A ).…”

Section: Resultssupporting

confidence: 92%

ENaC in Cholinergic Brush Cells

Kandel

Schmidt

Perniss

et al. 2018

Front. Cell Dev. Biol.

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Cholinergic polymodal chemosensory cells in the mammalian urethra (urethral brush cells = UBC) functionally express the canonical bitter and umami taste transduction signaling cascade. Here, we aimed to determine whether UBC are functionally equipped for the perception of salt through ENaC (epithelial sodium channel). Cholinergic UBC were isolated from ChAT-eGFP reporter mice (ChAT = choline acetyltransferase). RT-PCR showed mRNA expression of ENaC subunits Scnn1a, Scnn1b, and Scnn1g in urethral epithelium and isolated UBC. Scnn1a could also be detected by next generation sequencing in 4/6 (66%) single UBC, two of them also expressed the bitter receptor Tas2R108. Strong expression of Scnn1a was seen in some urothelial umbrella cells and in 65% of UBC (30/46 cells) in a Scnn1a reporter mouse strain. Intracellular [Ca2+] was recorded in isolated UBC stimulated with the bitter substance denatonium benzoate (25 mM), ATP (0.5 mM) and NaCl (50 mM, on top of 145 mM Na+ and 153 mM Cl− baseline in buffer); mannitol (150 mM) served as osmolarity control. NaCl, but not mannitol, evoked an increase in intracellular [Ca2+] in 70% of the tested UBC. The NaCl-induced effect was blocked by the ENaC inhibitor amiloride (IC50 = 0.47 μM). When responses to both NaCl and denatonium were tested, all three possible positive response patterns occurred in a balanced distribution: 42% NaCl only, 33% denatonium only, 25% to both stimuli. A similar reaction pattern was observed with ATP and NaCl as test stimuli. About 22% of the UBC reacted to all three stimuli. Thus, NaCl evokes calcium responses in several UBC, likely involving an amiloride-sensitive channel containing α-ENaC. This feature does not define a new subpopulation of UBC, but rather emphasizes their polymodal character. The actual function of α-ENaC in cholinergic UBC—salt perception, homeostatic ion transport, mechanoreception—remains to be determined.

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Section: Resultssupporting

confidence: 92%

ENaC in Cholinergic Brush Cells

Kandel

Schmidt

Perniss

et al. 2018

Front. Cell Dev. Biol.

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“…The urinary bladder mucosa (UBM), which lines the inner surface of the renal pelvis, ureters and bladder, forms a high‐resistance barrier and functions as an integral part of a “sensory web” which receives, amplifies, and transmits information about its external milieu . There is increasing evidence that the UBM plays an active role in both solute and fluid reabsorption and is able to modify urine composition . While the underlying biochemical mechanisms have yet to be clarified, it is known that the UBM expresses a variety of receptors and channels including several types of aquaporin water channels and the renal epithelial sodium channel (ENaC), both of which play important roles in vasopressin‐mediated water homeostasis in the kidney .…”

Section: Introductionmentioning

confidence: 99%

Aging increases the expression of vasopressin receptors in both the kidney and urinary bladder

Birder

Jackson

Wein

et al. 2018

Neurourology and Urodynamics

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Aims: The goal of this study was to determine whether aging effects the expression of V 1a and V 2 vasopressin receptors in the urinary bladder mucosa (UBM) and kidney. Methods: UBM and kidneys were obtained from young (3 months-of-age) and old (25-30 months-of-age) female Fisher 344 rats. Tissue samples were analyzed by western blotting for V 1a and V 2 receptor expression, and rat plasma levels of vasopressin levels were measured by ELISA. Results: V 1a and V 2 receptors were detected in both the UBM and kidneys. Aging significantly (P < 0.05) increased the expression of V 2 receptors by 2.80 ± 0.52 and Neurourology and Urodynamics. 2019;38:393-397.wileyonlinelibrary.com/journal/nau

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“…Therefore, there is increasing evidence that the urothelium plays an active role in both solute and fluid reabsorption and is able to modify the final composition of urine. [4][5][6][7][8] Transurothelial water transport is facilitated by channels called aquaporins (AQP). Several AQP family proteins (AQP1, 2, 3, 4, 7, 9, and 11) are differentially expressed in the mammalian urothelium, including mouse, rat, pig, and human.…”

Section: In Mediating Transuroepithelial Water and Solute Transfermentioning

confidence: 99%

“…In the process, a temporary reduction in bladder volume occurs without micturition, which is suggestive of water resorption from the bladder. Therefore, there is increasing evidence that the urothelium plays an active role in both solute and fluid reabsorption and is able to modify the final composition of urine 4–8 …”

Section: The Role Of Urothelium In Mediating Transuroepithelial Water...mentioning

confidence: 99%

“…The urothelium maintains an effective barrier to preserve underlying tissues from the hostile environment of urine. However, the urothelium also has the capacity to transport salt and water transport that has the capacity to diminish bladder volume, 7 but it is unknown if this function is subject to circadian variation. A sensation of bladder volume and composition is mediated by stretch‐dependent neuromodulator releases, such as adenosine triphosphate (ATP) and acetylcholine (ACh) 19,20 .…”

Section: Circadian Rhythms Of Bladder Function Relevance To Nocturiamentioning

confidence: 99%

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ICI‐RS 2019 nocturia think tank: How can experimental science guide us in understanding the pathophysiology of nocturia?

Vahabi

Jabr

Fry

et al. 2020

Neurourology and Urodynamics

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Introduction The following is a report on the proceedings of the 2019 International Consultation on Incontinence‐Research Society nocturia think tank (NTT). Objectives The objectives of the 2019 NTT were as follows: (a) to evaluate the role of urothelium in the pathophysiology of nocturia; (b) to determine whether nocturia is a circadian disorder; (c) to discuss the role of melatonin in nocturia; (d) to consider ambulatory urodynamic monitoring in evaluating patients with nocturia; (e) to explore studies of water handling in human compartments utilizing heavy water; and (f) to explore whether basic science is the key to understanding the treatment options for diminished bladder capacity in patients with nocturia. Methods A compendium of discussions of the role of experimental science in understanding the pathophysiology of nocturia is described herein. Results and Conclusions Translational science will play an increasing role in understanding the pathophysiology of nocturia, which may result in improved treatment strategies.

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Is electrolyte transfer across the urothelium important?: ICI‐RS 2015

Abstract: The phenomenon of urine modification by the urothelium may be physiologically important during normal bladder filling. Research should be focused on investigating how this may change in conditions of urinary dysfunction.

Cited by 4 publications

References 42 publications

ENaC in Cholinergic Brush Cells

ENaC in Cholinergic Brush Cells

Aging increases the expression of vasopressin receptors in both the kidney and urinary bladder

ICI‐RS 2019 nocturia think tank: How can experimental science guide us in understanding the pathophysiology of nocturia?

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