MP62-09 DETRUSOR RELAXATION MEDIATED BY ACTIVATION OF THE SUCCINATE RECEPTOR GPR91.
Bibliographic record
Abstract
You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP62)1 Apr 2019MP62-09 DETRUSOR RELAXATION MEDIATED BY ACTIVATION OF THE SUCCINATE RECEPTOR GPR91. Abubakr Mossa, Monica Velasquez-Flores, Philippe Cammisotto, and Lysanne Campeau* Abubakr MossaAbubakr Mossa More articles by this author , Monica Velasquez-FloresMonica Velasquez-Flores More articles by this author , Philippe CammisottoPhilippe Cammisotto More articles by this author , and Lysanne Campeau*Lysanne Campeau* More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556832.17091.fcAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: The bladder urothelium and detrusor layer express the succinate receptor, GPR91. The acute and immediate effects of its activation on bladder function have yet been described. The aim of this study is to demonstrate the acute effect of succinate activation of its receptor GPR91 on bladder contraction/relaxation using a mouse model with specific deletion of the GPR91 receptor. METHODS: Conscious cystometry was carried out on C57Bl6 and GPR91(-/-) mice with and without succinate intravesical instillation. Contractile properties of bladder strips from the 2 strains were analyzed by organ bath. Characteristics of bladder were analyzed by Masson's trichrome and immunoblotting. Primary urothelial cell culture from both groups were investigated for nitric oxide secretion (colorimetric assay), ATP and cGMP levels (commercial kits). RESULTS: The body weight was similar between GPR91(-/-) and C57Bl6 mice, while the bladder mass was higher in GPR91(-/-) mice. Masson's trichrome revealed a thicker urothelium and lamina propria in GPR91(-/-) mice. Conscious cystometry showed that GPR91(-/-) mice had a lower bladder capacity, lower micturition volume and lower intercontraction interval. Intravesical instillation of succinate (10 mM) increased the bladder capacity in C57Bl6 mice only. In organ bath, bladder strips from C57Bl6 and GPR91(-/-) mice had similar contractions elicited by potassium chloride ,carbachol and electrical field stimulation. Succinate administration relaxed carbachol-stimulated strips in C57Bl6 mice only. In vitro, short-term secretion of nitric oxide by urothelial cells from C57Bl6 and KO mice were similar at all concentrations (from 200 µM to 10 mM), confirming that nitric oxide is not involved in relaxation elicited by succinate. Succinate did not affect cGMP levels either in cell culture but decreased ATP released into the culture medium. CONCLUSIONS: These results suggest that succinate modulates the relaxation-contraction of the detrusor through its action on its receptor GPR91, possibly by decreasing ATP synthesis in the urothelium. Source of Funding: This research was funded by the FRQS. Montreal, Canada© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e890-e890 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Abubakr Mossa More articles by this author Monica Velasquez-Flores More articles by this author Philippe Cammisotto More articles by this author Lysanne Campeau* More articles by this author Expand All Advertisement PDF downloadLoading ...
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.031 | 0.005 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".