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Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.

Ekman, Mari LU ; Rippe, Catarina LU ; Sadegh, Mardjaneh Karbalaei; Dabestani, Saeed; Mörgelin, Matthias LU ; Uvelius, Bengt LU and Swärd, Karl LU (2012) In European Journal of Pharmacology 683(1-3). p.238-245
Abstract
Caveolae are 50-100nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M(3) receptors and the K(ATP) channel subunit Kir6.1 are associated with human detrusor caveolae, and to pharmacologically assess the relevance of this organization for contractility. Detrusor strips were dissected and used in ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by cholesterol desorption using mβcd (methyl-β-cyclodextrin). Mβcd disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of the concentration-response curve for the muscarinic receptor agonist carbachol. The effect of mβcd was inhibited by the K(ATP) blockers... (More)
Caveolae are 50-100nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M(3) receptors and the K(ATP) channel subunit Kir6.1 are associated with human detrusor caveolae, and to pharmacologically assess the relevance of this organization for contractility. Detrusor strips were dissected and used in ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by cholesterol desorption using mβcd (methyl-β-cyclodextrin). Mβcd disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of the concentration-response curve for the muscarinic receptor agonist carbachol. The effect of mβcd was inhibited by the K(ATP) blockers glibenclamide, repaglinide and PNU-37883, and it was mimicked by the K(ATP) activator levcromakalim. Immunoelectron microscopy showed muscarinic M(3) receptors and Kir6.1 to be enriched in caveolae. In conclusion, pharmacological K(ATP) channel inhibition antagonizes the effect of caveolae disruption on muscarinic contractility in the human detrusor, and the K(ATP) channel subunit Kir6.1 co-localizes with M(3) receptors in caveolae. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Detrusor, Carbachol, Glibenclamide, Cyclodextrin, Smooth muscle
in
European Journal of Pharmacology
volume
683
issue
1-3
pages
238 - 245
publisher
Elsevier
external identifiers
  • wos:000303436200033
  • pmid:22410194
  • scopus:84860452017
ISSN
1879-0712
DOI
10.1016/j.ejphar.2012.02.039
language
English
LU publication?
yes
id
bb81e113-aaeb-4459-9c0e-29c8582cb4a9 (old id 2431916)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22410194?dopt=Abstract
date added to LUP
2012-04-03 10:29:35
date last changed
2017-02-22 11:43:58
@article{bb81e113-aaeb-4459-9c0e-29c8582cb4a9,
  abstract     = {Caveolae are 50-100nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M(3) receptors and the K(ATP) channel subunit Kir6.1 are associated with human detrusor caveolae, and to pharmacologically assess the relevance of this organization for contractility. Detrusor strips were dissected and used in ultrastructural, biochemical and mechanical studies. Caveolae were manipulated by cholesterol desorption using mβcd (methyl-β-cyclodextrin). Mβcd disrupted caveolae and caused a cholesterol-dependent ~3-fold rightward shift of the concentration-response curve for the muscarinic receptor agonist carbachol. The effect of mβcd was inhibited by the K(ATP) blockers glibenclamide, repaglinide and PNU-37883, and it was mimicked by the K(ATP) activator levcromakalim. Immunoelectron microscopy showed muscarinic M(3) receptors and Kir6.1 to be enriched in caveolae. In conclusion, pharmacological K(ATP) channel inhibition antagonizes the effect of caveolae disruption on muscarinic contractility in the human detrusor, and the K(ATP) channel subunit Kir6.1 co-localizes with M(3) receptors in caveolae.},
  author       = {Ekman, Mari and Rippe, Catarina and Sadegh, Mardjaneh Karbalaei and Dabestani, Saeed and Mörgelin, Matthias and Uvelius, Bengt and Swärd, Karl},
  issn         = {1879-0712},
  keyword      = {Detrusor,Carbachol,Glibenclamide,Cyclodextrin,Smooth muscle},
  language     = {eng},
  number       = {1-3},
  pages        = {238--245},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2012.02.039},
  volume       = {683},
  year         = {2012},
}