Biomechanical properties and innervation of the female caveolin-1-deficient detrusor.
(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:
https://lup.lub.lu.se/record/1731763
- author
- 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
- organization
- publishing date
- 2011
- 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}}, }