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IC/BPS-associated alterations of M2 and M3 muscarinic acetylcholine receptor trafficking in human detrusor.
Berndt-Paetz, Mandy; Herbst, Luise; Weimann, Annett; Gonsior, Andreas; Stolzenburg, Jens-Uwe; Neuhaus, Jochen.
Afiliación
  • Berndt-Paetz M; Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany.
  • Herbst L; Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany.
  • Weimann A; Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany.
  • Gonsior A; Department of Urology, University Hospital Leipzig AöR, Leipzig, Germany.
  • Stolzenburg JU; Department of Urology, University Hospital Leipzig AöR, Leipzig, Germany.
  • Neuhaus J; Department of Urology, Research Laboratories, University of Leipzig, Leipzig, Germany.
Neurourol Urodyn ; 38(7): 1818-1827, 2019 09.
Article en En | MEDLINE | ID: mdl-31301091
AIMS: To explore caveolae- and clathrin-mediated internalization of muscarinic M2 and M3 receptors, recycling and degradation in formalin-fixed paraffin-embedded detrusor sections; to study alterations possibly involved in the pathophysiology of the bladder functional disorder, interstitial cystitis/bladder pain syndrome (IC/BPS). MATERIALS AND METHODS: Samples of IC/BPS (n = 11) and cystectomy patients (n = 11) were analyzed. Proximity ligation assay (PLA) was used to detect interactions of M2 and M3 with endocytotic regulators (Cav-1, clathrin, Rab7, and Rab11) by Cy3 labeling. Analyses of three-dimensional (3D)-reconstructed z-stacks (63 × Oil 1.4) were done with Huygens software. We determined the object density for quantification and assessed membrane localization. RESULTS: Receptor/protein complexes were detected as well-demarcated 3D objects. Interactions of M2 with Cav-1, clathrin, Rab11, and Rab7 were significantly increased in IC/BPS. M3/clathrin and M3/Rab11 complexes were higher in IC/BPS, while M3/Cav-1 and M3/Rab7 were not. A significant shift of complexes from the membrane to cytoplasm was observed in conjunction with increased internalization via clathrin vesicles or caveolae in IC/BPS. CONCLUSIONS: High numbers of M3/clathrin and M3/Rab11 complexes reflect the well-documented clathrin-mediated desensitization of M3 and speak in favor with enhanced receptor protein expression in IC/BPS. Increased amounts of M2/Cav-1, M2/clathrin, and M2/Rab11 complexes represent altered M2 internalization and recycling leading to high abundance in IC/BPS. In this regard, caveolae-localized M2 could be possibly associated with the activation of nitric oxide (NO) synthase and NO production.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vejiga Urinaria / Cistitis Intersticial / Receptor Muscarínico M2 / Receptor Muscarínico M3 Tipo de estudio: Risk_factors_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Neurourol Urodyn Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vejiga Urinaria / Cistitis Intersticial / Receptor Muscarínico M2 / Receptor Muscarínico M3 Tipo de estudio: Risk_factors_studies Límite: Aged / Female / Humans / Middle aged Idioma: En Revista: Neurourol Urodyn Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos