Association of muscarinic M₃ receptors and Kir6.1 with caveolae in human detrusor muscle.
| Title | Association of muscarinic M₃ receptors and Kir6.1 with caveolae in human detrusor muscle. |
| Publication Type | Journal Article |
| Year of Publication | 2012 |
| Authors | Ekman, M, Rippe C, Sadegh MK, Dabestani S, Mörgelin M, Uvelius B, Swärd K |
| Journal | European journal of pharmacology |
| Volume | 683 |
| Issue | 1-3 |
| Pagination | 238-45 |
| Date Published | 2012 May 15 |
| ISSN | 1879-0712 |
| Keywords | Aged, ATP-Binding Cassette Transporters, beta-Cyclodextrins, Caveolae, Female, Gene Expression, Humans, KATP Channels, Male, Membrane Transport Modulators, Muscarinic Agonists, Muscle Contraction, Muscle, Smooth, Potassium Channels, Inwardly Rectifying, Protein Isoforms, Protein Subunits, Protein Transport, Receptor, Muscarinic M3, Receptors, Drug, RNA, Messenger, Urinary Bladder |
| Abstract | Caveolae are 50-100 nm large membrane invaginations that play a role in cellular signaling. The aim of the present study was to assess whether muscarinic M₃ 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 M₃ 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 M₃ receptors in caveolae. |
| DOI | 10.1016/j.ejphar.2012.02.039 |
| Alternate Journal | Eur. J. Pharmacol. |