Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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

Sadegh, Mardjaneh Karbalaei ; Ekman, Mari LU ; Rippe, Catarina LU ; Sundler, Frank LU ; Wierup, Nils LU ; Mori, Michiko LU ; Uvelius, Bengt LU and Swärd, Karl LU (2011) In British Journal of Pharmacology Dec. p.1156-1170
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Pharmacology
volume
Dec
pages
1156 - 1170
publisher
Wiley
external identifiers
  • wos:000286668500013
  • pmid:21091642
  • scopus:79551494259
ISSN
1476-5381
DOI
10.1111/j.1476-5381.2010.01115.x
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Neuroendocrine Cell Biology (013212008), Cellular Biomechanics (013212075), Department of Urology, Lund (013077000), Airway Inflammation and Immunology (013212038)
id
59bed065-013a-488c-b820-5328b6216b23 (old id 1731763)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21091642?dopt=Abstract
date added to LUP
2016-04-04 09:24:02
date last changed
2022-02-28 07:47:10
@article{59bed065-013a-488c-b820-5328b6216b23,
  abstract     = {{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.}},
  author       = {{Sadegh, Mardjaneh Karbalaei and Ekman, Mari and Rippe, Catarina and Sundler, Frank and Wierup, Nils and Mori, Michiko and Uvelius, Bengt and Swärd, Karl}},
  issn         = {{1476-5381}},
  language     = {{eng}},
  pages        = {{1156--1170}},
  publisher    = {{Wiley}},
  series       = {{British Journal of Pharmacology}},
  title        = {{Biomechanical properties and innervation of the female caveolin-1-deficient detrusor.}},
  url          = {{http://dx.doi.org/10.1111/j.1476-5381.2010.01115.x}},
  doi          = {{10.1111/j.1476-5381.2010.01115.x}},
  volume       = {{Dec}},
  year         = {{2011}},
}