PhD Scientific Days 2026

Poster Session 3.J - Theoretical and Translational Medicine

The Role of TRPV4 in the Development of Urinary Bladder Hyperactivity

Name of the presenter

Cserny, Anna Vilma

Institute/workplace of the presenter

Semmelweis University, Institute of Clinical Pathophysiology

Authors

Anna Vilma Cserny¹
1: Semmelweis University, Institute of Clinical Pathophysiology

Text of the abstract

Introduction: The etiology of overactive bladder (OAB) syndrome remains unclear. However, sensory dysfunction of the urinary bladder has been implicated, and literature suggests increased activity of the Transient Receptor Potential Vanilloid-4 (TRPV4) ion channel in bladder samples from patients suffering from OAB.
Aims: We aimed to analyze the intracellular signaling pathways of TRPV4 receptors in the urinary bladder (UB) with the goal of better understanding the intracellular regulation of micturition and identifying potential novel therapeutic targets of OAB.
Methods: Experiments were conducted on adult male and female (C57Bl6/N) mice. Intravesical pressure changes were measured in vivo using transurethral cystometry; volume parameters were normalized to the maximum bladder volume determined by body weight. The magnitude of contractile forces in bladder strips was recorded ex vivo using a myograph. The release of prostaglandin E₂ (PGE₂) and thromboxane A₂ (TXA₂) from bladder samples was quantified by ELISA.
Results: Intravesical administration of the TRPV4 agonist GSK1016790A (GSK) significantly increased bladder activity in vivo. This effect was abolished following pretreatment with intraperitoneal indomethacin: the first voiding contraction occurred at significantly lower bladder volumes. Furthermore, bladder capacity decreased, while voiding frequency increased. Ex vivo, the TRPV4 agonist, GSK induced contractions that were significantly reduced by indomethacin pretreatment. In COX1-KO bladder strips pretreated with a COX2 inhibitor, the GSK-induced contraction was completely abolished. In addition, elevated levels of TXA₂ and PGE₂ release were measured in GSK-treated bladder samples. . EP1 and EP3 antagonists were ineffective, whereas the TP-receptor antagonist SQ29548 markedly reduced GSK-induced contractions.
Conclusion: In summary, activation of the TRPV4 ion channel significantly increases bladder activity in a COX-enzyme-dependent manner, associated with a substantial release of PGE₂ and TXA₂. The TP receptor plays a primary role in mediating direct detrusor contraction. The TRPV4–COX–TP signaling pathway identified here may represent a novel potential therapeutic target for the development of pharmacological treatments for patients with OAB.
Funding: NKFIH K-135683, K-139230, Advanced-151053, TKP2021-EGA-25, and 2025-2.1.1-EKÖP-2025-00014.