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Bladder Smooth Muscle Strip Contractility as a Method to Evaluate Lower Urinary Tract Pharmacology
Published on: August 18, 2014
Modulation of bladder function by prostaglandin EP3 receptors in the central nervous system
Xin Su1, Lisa A Leon, Charlene W Wu
1GlaxoSmithKline Pharmaceuticals, Department of Urology, 709 Swedeland Rd., King of Prussia, PA 19406-0939, USA.
American Journal of Physiology. Renal Physiology
|July 18, 2008
Summary
Central Prostaglandin EP3 receptor antagonists (DG041 and CM9) reduce bladder overactivity and pain. These findings suggest EP3 antagonists may treat bladder disorders by acting on spinal and supraspinal centers.
Area of Science:
- Neuroscience
- Pharmacology
- Urology
Background:
- Prostaglandin EP3 receptors in the central nervous system (CNS) may influence urinary bladder function by modulating afferent pathways.
- Understanding the role of EP3 receptors in bladder control is crucial for developing treatments for overactive bladder and bladder pain.
Purpose of the Study:
- To investigate the effects of selective EP3 receptor antagonists, DG041 and CM9, on urinary bladder function and nociception in rats.
- To determine the potential of centrally acting EP3 antagonists in managing detrusor overactivity and bladder pain.
Main Methods:
- Selective EP3 antagonists DG041 and CM9 were synthesized and characterized using radioligand binding and functional FLIPR assays.
- The effects of intrathecal and intracerebroventricular administration of DG041 and CM9 on volume-induced bladder contractions and visceromotor reflex (VMR) were evaluated in female rats.
Main Results:
- DG041 and CM9 demonstrated high affinity and selectivity for EP3 receptors, inhibiting calcium influx.
- Both antagonists dose-dependently reduced the frequency of bladder contractions after central administration.
- Intrathecal administration of DG041 and CM9 produced a long-lasting inhibition of VMR, while intracerebroventricular administration resulted in transient VMR reduction.
Conclusions:
- EP3 receptors play a significant role in regulating bladder micturition at both spinal and supraspinal levels.
- EP3 receptors are implicated in spinal cord-mediated bladder nociception.
- Centrally acting EP3 receptor antagonists show promise for treating detrusor overactivity and bladder pain.
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