Association of muscarinic M(3) receptors and Kir6.1 with caveolae in human detrusor muscle.
Author
Summary, in English
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.
Publishing year
2012
Language
English
Pages
238-245
Publication/Series
European Journal of Pharmacology
Volume
683
Issue
1-3
Full text
Links
Document type
Journal article
Publisher
Elsevier
Topic
- Pharmacology and Toxicology
Keywords
- Detrusor
- Carbachol
- Glibenclamide
- Cyclodextrin
- Smooth muscle
Status
Published
Research group
- Cellular Biomechanics
- Urology
ISBN/ISSN/Other
- ISSN: 1879-0712