PhD Scientific Days 2024

Theoretical and Translational Medicine III.

The Mechanosensory Transient Receptor Potential Vanilloid 4 Exerts Its Effects Through Prostanoids in the Urinary Bladder

Előadó neve

Dr. Lénárt, Ádám

Neptun code

WZU7TJ

Előadó munkahelye

Institute of Translational Medicine

Előadó telefonszáma

06306309988

Előadó e-mail címe

lenartadam15@gmail.com

Az előadás címe

The Mechanosensory Transient Receptor Potential Vanilloid 4 Exerts Its Effects Through Prostanoids in the Urinary Bladder

Szerző(k) neve és munkahelye

Ádám Lénárt¹, Kinga Borsodi¹, Helga Balla¹, Péter Molnárt József², Bálint Dér², Péter Nyirády², Zoltán Benyó¹

1: Institute of Translational Medicine
2: Department of Urology

Bemutatás módja

Szóbeli

Szekció

Theoretical and Translational Medicine III.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Overactive bladder syndrome (OAB) is a common urological condition that significantly affects the lives of those affected. The commonly used drugs in treatment have numerous side effects, and their effectiveness often falls short of expectations. The exact pathomechanism of OAB is unknown; however, some theories suggest that dysfunction in the bladder's sensory function may be involved. The Transient Receptor Potential Vanilloid 4 (TRPV4) is an ion channel widely present in the bladder wall, responsible for sensing bladder fullness. Abnormal functioning of TRPV4 may be responsible for altered bladder sensation.
We aim to clarify the signaling pathways of TRPV4-mediated mechanosensation to gain a better understanding of the regulation of micturition and to identify potential novel therapeutic targets for its disorders.
We used 90-120 days old female/male C57Bl/6 and genetically modified [cyclooxygenase-1 knockout (COX-1 KO)] mice. In cystometry, we measured the changes in intravesical pressure during bladder filling. Bladder contractions were measured via myography in isolated mouse bladders. We performed ELISA assays to measure prostanoid levels in bladder samples.
Filling the bladder with a TRPV4 agonist resulted in significant bladder activation, an effect that was inhibited in the presence of intraperitoneally administered indomethacin. In COX-1 KO animals, filling the bladder with the TRPV4 agonist resulted in milder activation compared to wild-type animals. During myography, the TRPV4 agonist induced contractions, an effect that was greatly reduced in the presence of indomethacin. Following TRPV4 agonist treatment, we measured significantly elevated levels of prostaglandin E2 from bladder samples.
Activation of the TRPV4 ion channel causes bladder hyperactivity, an effect primarily mediated by the inflammatory mediator prostaglandin E2. In COX-1 KO animals, the activating effect of TRPV4 did not completely disappear, suggesting that the COX-2 enzyme may also play a role. Activation of TRPV4 induces bladder contractions independent of neural reflexes. By inhibiting the synthesis of prostaglandin E2, we were able to eliminate the bladder-activating effect of TRPV4. Identifying this pathway may provide potential targets for treating voiding disorders.
K-125174,K-135683,K-139230,PD-132851,2020-1.1.6-JÖVŐ-2021-00010,TKP2021-EGA-25,EFOP-3.6.3-VEKOP-16-2017-00009

University

Semmelweis University

Supervisor

Prof. Dr. Zoltán Benyó

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8254

Start

15:30

End

15:40