Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.
Författare
Summary, in English
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.
Publiceringsår
2010
Språk
Engelska
Sidor
142-148
Publikation/Tidskrift/Serie
European Journal of Pharmacology
Volym
634
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Pharmacology and Toxicology
Status
Published
Forskningsgrupp
- Molecular Vascular Physiology
- Airway Inflammation and Immunology
- Urology
ISBN/ISSN/Övrigt
- ISSN: 1879-0712