Bladder Contraction and Relaxation
The primary function of the bladder is to store urine before micturition. Proper coordination between urinary bladder contraction/relaxation is essential for normal filling and emptying. Alterations in these processes can lead to lower urinary tract disorders such as urinary incontinence, overactive bladder, bladder hypertrophy, and bladder underactivity.
At REPROCELL, one of our key areas of expertise is the assessment of smooth muscle contraction/relaxation in fresh, functional human bladder tissues. We source bladder tissue multiple times a month, allowing us to evaluate the efficacy of your novel compounds in both normal and overactive bladder conditions.
Our team can assess the effect of your test article on detrusor muscle tone using fresh, functional bladder tissues. With the ability to determine both EC/IC50 and pA2 values, our assays provide comprehensive insights into the pharmacological activity of your compounds.
Image: Example of fresh bladder tissue used in our bladder contractility studies.
Our Capabilities Include:
- Electrical Field Stimulation (EFS): This method is employed to activate nerves that induce bladder contraction, providing valuable data on neural control of urinary bladder contraction/relaxation.
- Reference Compounds: Our validated assays use reference compounds such as carbachol, isoproterenol, oxybutynin (an anti-muscarinic used for treating overactive bladder), and retigabine to ensure reliable comparisons.
- Organ Bath and Ussing Chamber Experiments: In these experiments, a section of intact bladder tissue remains fully functional for up to 16 hours. This setup allows for detailed assessment of drug transporters, ion channels, and secretory processes, providing an extended window for in-depth evaluation.
- Functional Tests: Bladder tissue samples, including isolated bladder strips, are attached to a sensitive transducer, enabling the detection of subtle changes in muscle tension. These functional assays help determine the contractile responses of the bladder to your test compounds.
Our protocols are highly flexible, ranging from exploratory non-GLP screening to full studies monitored for GLP compliance. With the use of validated reference compounds and advanced techniques, we deliver robust data on smooth muscle contraction/relaxation to support your drug discovery and development efforts.
Image: Partially dissected human bladder showing smooth muscle bundles after removal of the urothelium.
Overactive Bladder Treatment and New Therapies
Overactive bladder (OAB) is a prevalent condition affecting over 400 million people globally, characterized by urinary urgency, frequency, nocturia, and sometimes urge incontinence. This syndrome significantly impacts quality of life, with effects comparable to chronic conditions like diabetes, rheumatoid arthritis, and asthma.
Current Treatment Guidelines
The International Continence Society (ICS) and American Urological Association (AUA) recommend a stepwise approach to OAB treatment, starting with lifestyle changes and bladder training. However, for many patients, pharmacological treatments are necessary.
- Antimuscarinic Agents: First-line pharmacologic therapy includes drugs such as oxybutynin, tolterodine, and solifenacin, which reduce bladder contractions by inhibiting M3 receptors. While effective, these drugs often lead to side effects like dry mouth, constipation, and blurred vision, as they lack selectivity for bladder-specific receptors.
- Beta-3 Agonists: Mirabegron is an alternative therapy for patients intolerant to antimuscarinics, promoting relaxation of the detrusor muscle during the storage phase without affecting voiding.
New Therapies and Research
Despite advancements, compliance with OAB treatments remains low, and pharmaceutical companies are investing in the development of more targeted therapies. Emerging treatments include:
- Botulinum Toxin (OnabotulinumtoxinA): Shown to reduce involuntary bladder contractions.
- Gene Therapy and Personalized Medicine: Experimental approaches aim to provide tailored treatments with fewer side effects.
At REPROCELL, our human tissue assays provide critical insights into how these therapies affect bladder function, supporting drug discovery efforts. With techniques like organ baths and Ussing chambers, we help evaluate the safety, efficacy, and pharmacokinetics of novel OAB treatments, considering interactions with the urothelium and underlying muscle layers.
Discover whether your test article affects bladder relaxation via adrenoceptors, with isoproterenol as a reference compound.
Discover whether your test article affects bladder contraction via muscarinic receptors, with carbachol as a reference compound.
Discover whether your test article affects bladder contraction induced by electrical field stimulation.