Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.
(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:
https://lup.lub.lu.se/record/2431916
- author
- Ekman, Mari LU ; Rippe, Catarina LU ; Sadegh, Mardjaneh Karbalaei ; Dabestani, Saeed ; Mörgelin, Matthias LU ; Uvelius, Bengt LU and Swärd, Karl LU
- organization
- publishing date
- 2012
- 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
- pmid:22410194
- 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
- 2016-04-01 10:15:07
- date last changed
- 2022-01-25 21:22:31
@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}}, keywords = {{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 = {{https://lup.lub.lu.se/search/files/1689616/2855907.pdf}}, doi = {{10.1016/j.ejphar.2012.02.039}}, volume = {{683}}, year = {{2012}}, }