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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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
British Journal of Pharmacology
volume
Dec
pages
1156 - 1170
publisher
The British Pharmacological Society
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
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
2010-12-01 12:58:47
date last changed
2016-10-13 04:29:50
@misc{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    = {ARRAY(0xb78e728)},
  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},
  volume       = {Dec},
  year         = {2011},
}