TRPA1 channel mediates methylglyoxal-induced mouse bladder dysfunction
Akila L Oliveira1, Matheus L Medeiros1, Erick de Toledo Gomes1
1Department of Pharmacology, University of Campinas (UNICAMP), São Paulo, Brazil.
Frontiers in Physiology
|December 25, 2023
Summary
Methylglyoxal (MGO) causes overactive bladder in mice by activating the TRPA1 channel. Blocking TRPA1 with HC-030031 reversed these bladder dysfunctions, suggesting a therapeutic target.
Area of Science:
- Urology
- Neuroscience
- Metabolism
Background:
- Hyperglycemia in diabetes leads to methylglyoxal (MGO) accumulation.
- MGO modulates the transient receptor potential ankyrin 1 channel (TRPA1).
- MGO exposure causes bladder dysfunction in mice.
Purpose of the Study:
- To investigate the role of TRPA1 in MGO-induced bladder dysfunction.
- To evaluate TRPA1 expression in mouse bladders after MGO exposure.
- To assess the therapeutic effect of a TRPA1 blocker on MGO-induced cystometric alterations.
Main Methods:
- Mice received MGO in drinking water for 12 weeks.
- TRPA1 expression and MGO adducts (MG-H1) were analyzed in bladder tissues.
- Void spot assays and cystometry were performed in MGO-treated mice.
- The TRPA1 blocker HC-030031 was administered intravesically.
Main Results:
- MGO exposure increased MG-H1 and TRPA1 protein levels in mouse bladders.
- MGO-treated mice exhibited an overactive bladder phenotype (increased voids, reduced volume).
- HC-030031 infusion reversed MGO-induced increases in voiding frequency and reduced bladder capacity.
Conclusions:
- TRPA1 channel activation is involved in methylglyoxal-induced overactive bladder.
- TRPA1 blockers show potential for treating diabetic bladder dysfunction associated with high MGO levels.
