Mouse Bladder Smooth Muscle Lack the Functional Active NMDAR.

Autor: Zhan Z; The School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, China.; Public Center of Experimental Technology, Model Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, China., Chen Z; Department of Urology, Neijiang First People's Hospital, Neijiang, Sichuan, China., Zheng X; The School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, China., Xie X; The School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, China.; Public Center of Experimental Technology, Model Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, China., Li G; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China., Chen H; The School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan, China.; Public Center of Experimental Technology, Model Animal and Human Disease Research of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, China.; Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.; Nucleic Acid Medicine of Luzhou Key Laboratory, Southwest Medical University, Luzhou, Sichuan, China.
Jazyk: angličtina
Zdroj: Neurourology and urodynamics [Neurourol Urodyn] 2024 Nov 18. Date of Electronic Publication: 2024 Nov 18.
DOI: 10.1002/nau.25631
Abstrakt: Aims: This study aimed to investigate the role of N-methyl-D-aspartate receptors (NMDARs) in bladder smooth muscle (BSM) function and their potential as therapeutic targets for overactive bladder conditions.
Methods: We employed a multi-faceted approach to assess NMDAR activity in BSM. Myography was used to evaluate the effects of NMDAR antagonists and agonists on BSM contraction. Calcium imaging was conducted to determine changes in intracellular calcium ions. We also analyzed single-cell RNA sequencing data to examine NMDAR subunit expression in bladder cell subpopulations from both human and mouse tissues. Immunofluorescence staining was performed to localize the obligate NMDAR subunit, GluN1, in mouse BSM.
Results: NMDAR agonists did not modulate BSM contractile force. NMDAR antagonists had varied effects: D-AP5 showed no impact, CGS-19755 significantly inhibited contraction at the highest concentration, and MK-801 enhanced contractile force in a concentration-dependent manner at EFS frequencies of 1, 2, and 5 Hz. Neither agonists nor antagonists, including MK-801, induced calcium ion shifts in BSM cells. Single-cell RNA sequencing revealed no NMDAR subunit expression in BSM cells from human or mouse tissues. Immunofluorescence confirmed GluN1 expression in pulmonary artery smooth muscle but not in BSM.
Conclusions: Our findings indicate the absence of functional active NMDARs in BSM, suggesting that the therapeutic benefits of NMDAR inhibition observed in vivo for treating overactive bladder are unlikely to be directly mediated through effects on the BSM itself. This highlights the need to explore alternative mechanisms or targets for therapeutic interventions in overactive bladder conditions.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: