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Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.

Shakirova, Yulia LU ; Mori, Michiko LU ; Ekman, Mari LU ; Erjefält, Jonas LU ; Uvelius, Bengt LU and Swärd, Karl LU (2010) In European Journal of Pharmacology 634. p.142-148
Abstract
Voiding is mediated by muscarinic receptors in urinary bladder smooth muscle cells. Lipid rafts and caveolae are cholesterol enriched membrane domains that modulate the activity of G protein-coupled receptors and second messenger systems. Conflicting findings regarding sensitivity of muscarinic signalling to cholesterol desorption, which perturbs lipid rafts and caveolae, have been reported, and no study has used human urinary bladder. Here, the dependence of human bladder muscarinic receptor signalling on plasma membrane cholesterol was examined. Nerve-mediated contraction, elicited by electrical field stimulation of human bladder strips, was impaired by desorption of cholesterol using methyl-beta-cyclodextrin, and the... (More)
Voiding is mediated by muscarinic receptors in urinary bladder smooth muscle cells. Lipid rafts and caveolae are cholesterol enriched membrane domains that modulate the activity of G protein-coupled receptors and second messenger systems. Conflicting findings regarding sensitivity of muscarinic signalling to cholesterol desorption, which perturbs lipid rafts and caveolae, have been reported, and no study has used human urinary bladder. Here, the dependence of human bladder muscarinic receptor signalling on plasma membrane cholesterol was examined. Nerve-mediated contraction, elicited by electrical field stimulation of human bladder strips, was impaired by desorption of cholesterol using methyl-beta-cyclodextrin, and the concentration-response curve for the muscarinic agonist carbachol was right-shifted. No effect of cholesterol desorption was observed in rat, and in mouse increased maximum contraction was seen. Expression of caveolin-1, PLC(beta1) and M(3) muscarinic receptors did not differ between species in a manner that would explain the differential sensitivity to cholesterol desorption. In human bladder, threshold depolarisation eliminated the difference between cyclodextrin-treated and control preparations. Contraction elicited by depolarisation per se was not affected. M(3) muscarinic receptors appeared clustered along plasma membrane profiles as shown by immunohistochemical staining of human bladder, but no redistribution in association with cholesterol reduction were seen. Thus, muscarinic receptor-induced contraction of the urinary bladder exhibits species-specific differences in its sensitivity to cholesterol desorption suggesting differential roles of lipid rafts/caveolae in muscarinic receptor signalling between species. (Less)
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type
Contribution to journal
publication status
published
subject
in
European Journal of Pharmacology
volume
634
pages
142 - 148
publisher
Elsevier
external identifiers
  • wos:000277554900021
  • pmid:20176011
  • scopus:77951205835
ISSN
1879-0712
DOI
10.1016/j.ejphar.2010.02.017
language
English
LU publication?
yes
id
f8cab807-e117-4397-bbd1-94bbeae97c93 (old id 1552356)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20176011?dopt=Abstract
date added to LUP
2010-03-03 13:15:09
date last changed
2018-06-24 04:47:34
@article{f8cab807-e117-4397-bbd1-94bbeae97c93,
  abstract     = {Voiding is mediated by muscarinic receptors in urinary bladder smooth muscle cells. Lipid rafts and caveolae are cholesterol enriched membrane domains that modulate the activity of G protein-coupled receptors and second messenger systems. Conflicting findings regarding sensitivity of muscarinic signalling to cholesterol desorption, which perturbs lipid rafts and caveolae, have been reported, and no study has used human urinary bladder. Here, the dependence of human bladder muscarinic receptor signalling on plasma membrane cholesterol was examined. Nerve-mediated contraction, elicited by electrical field stimulation of human bladder strips, was impaired by desorption of cholesterol using methyl-beta-cyclodextrin, and the concentration-response curve for the muscarinic agonist carbachol was right-shifted. No effect of cholesterol desorption was observed in rat, and in mouse increased maximum contraction was seen. Expression of caveolin-1, PLC(beta1) and M(3) muscarinic receptors did not differ between species in a manner that would explain the differential sensitivity to cholesterol desorption. In human bladder, threshold depolarisation eliminated the difference between cyclodextrin-treated and control preparations. Contraction elicited by depolarisation per se was not affected. M(3) muscarinic receptors appeared clustered along plasma membrane profiles as shown by immunohistochemical staining of human bladder, but no redistribution in association with cholesterol reduction were seen. Thus, muscarinic receptor-induced contraction of the urinary bladder exhibits species-specific differences in its sensitivity to cholesterol desorption suggesting differential roles of lipid rafts/caveolae in muscarinic receptor signalling between species.},
  author       = {Shakirova, Yulia and Mori, Michiko and Ekman, Mari and Erjefält, Jonas and Uvelius, Bengt and Swärd, Karl},
  issn         = {1879-0712},
  language     = {eng},
  pages        = {142--148},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2010.02.017},
  volume       = {634},
  year         = {2010},
}