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Nils Wierup

Nils Wierup

Senior lecturer

Nils Wierup

Biomechanical properties and innervation of the female caveolin-1-deficient detrusor.

Author

  • Mardjaneh Karbalaei Sadegh
  • Mari Ekman
  • Catarina Rippe
  • Frank Sundler
  • Nils Wierup
  • Michiko Mori
  • Bengt Uvelius
  • Karl Swärd

Summary, in English

Background and purpose: Caveolin-1-deficiency is associated with substantial urogenital alterations. Here, a mechanical, histological and biochemical characterization of female detrusors from wild-type (WT) and caveolin-1-deficient (KO) mice was made to increase the understanding of detrusor changes caused by lack of caveolae. Experimental approach: Length-tension relationships were generated, and we recorded responses to electrical field stimulation (EFS), the muscarinic receptor agonist carbachol, and the purinoceptor agonist ATP. Tyrosine nitration and the contents of caveolin-1, cavin-1, muscarinic M(3) receptors, phospholipase C(β1) (PLC(β1) ), muscle-specific kinase (MuSK), and L-type Ca(2+) -channels were determined by immunoblotting. Innervation was assessed by immunohistochemistry. Key results: Bladder to body weight ratio was not changed, nor was there any change in the optimum circumference for force development. Depolarization- and ATP-induced stress was reduced, as was carbachol-induced stress between 0.1 and 3 µM, but the supramaximal relative (% K(+) ) response to carbachol was increased, as was M(3) expression. The scopolamine-sensitive component of the EFS-response was impaired, and yet bladder nerves contained little caveolin-1. The density of cholinergic nerves was unchanged, whereas CART- and CGRP-positive nerves were reduced. Immunoblotting revealed loss of MuSK. Conclusions and implications: Ablation of caveolae in the female detrusor leads to generalised impairment of contractility, ruling out prostate hypertrophy as a contributing factor. Cholinergic neuroeffector transmission is impaired without conspicuous changes in the density of cholinergic nerves or morphology of their terminals, but correlating with reduced expression of MuSK.

Department/s

  • Cellular Biomechanics
  • Department of Experimental Medical Science
  • Airway Inflammation and Immunology
  • Urology
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2011

Language

English

Pages

1156-1170

Publication/Series

British Journal of Pharmacology

Volume

Dec

Document type

Journal article

Publisher

Wiley

Topic

  • Pharmacology and Toxicology

Status

Published

Research group

  • Cellular Biomechanics
  • Airway Inflammation and Immunology
  • Urology

ISBN/ISSN/Other

  • ISSN: 1476-5381