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A Decentralized Ex Vivo Murine Bladder Model with the Detrusor Muscle Removed for Direct Access to the Suburothelium during Bladder Filling
Published on: November 28, 2019
Purinergic signalling in the urinary bladder
1AIAS, Aarhus Institute of Advanced Studies, Aarhus University, Denmark.
Adenosine triphosphate (ATP) released from the bladder urothelium activates sensory nerves, initiating the voiding reflex. Understanding urothelial ATP release mechanisms and receptors may lead to new treatments for lower urinary tract disorders.
Area of Science:
- Urology
- Neuroscience
- Cell Biology
Background:
- Parasympathetic neurons release ATP, contributing to bladder contraction.
- The bladder urothelium also releases ATP in response to mechanical stretch and chemical mediators.
- Urothelial ATP plays a crucial role in bladder function and sensory signaling.
Purpose of the Study:
- To elucidate the mechanisms of urothelial ATP release.
- To identify the receptors activated by urothelial ATP.
- To explore the therapeutic potential of targeting urothelial ATP pathways for lower urinary tract disorders.
Main Methods:
- Investigated ATP release from urothelial cells via vesicular exocytosis and pannexin hemichannel activity.
- Examined the activation of P2X3 and P2X2/3 receptors on sensory nerves by released ATP.
- Studied the effects of ATP on suburothelial interstitial cells and their role in signal propagation.
Main Results:
- Urothelial ATP release occurs through vesicular exocytosis and, to a lesser extent, pannexin hemichannels.
- Released ATP activates P2X3 and P2X2/3 receptors on sensory nerves, mediating the voiding reflex and sensation.
- ATP also influences interstitial cells, potentially spreading signals to the detrusor muscle.
Conclusions:
- Urothelial ATP is a key mediator in bladder function, sensory signaling, and the voiding reflex.
- Dysregulation of urothelial ATP release is implicated in urological diseases like interstitial cystitis.
- Targeting urothelial ATP release mechanisms and receptors presents a promising therapeutic strategy for lower urinary tract disorders.
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