| 1. |
- Shakirova, Yulia, et al.
(författare)
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Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.
- 2010
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 649, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- Organ hypertrophy is often found to be associated with changes in the expression of caveolins and altered density of caveolae in the membrane. A plethora of signalling intermediaries are associated with caveolae and loss of caveolae has profound effects on contractility of the urinary bladder. We hypothesized that smooth muscle hypertrophy caused by bladder outflow obstruction (BOO) might lead to an altered caveola density with consequences for contractile regulation. Rat BOO for 6weeks caused a 2.56-fold increase in the number of smooth muscle caveolae per μm membrane. No changes in the expression of caveolin-1 or cavin-1, normalized to β-actin were seen, but membrane area per unit muscle volume dropped to 0.346. Hypertrophy was associated with altered contraction in response to carbachol. The effect on contraction of cholesterol desorption, which disrupts lipid rafts and caveolae, was however not changed. Contraction in response to bradykinin resisted mβcd in control destrusor, but was inhibited by it after 6weeks of obstruction. It is concluded that rat detrusor hypertrophy leads to an increased number of caveolae per unit membrane area. This change is due to a reduction of membrane area per volume muscle and it does not play a role for cholinergic activation, but promotes contraction in response to bradykinin after long-term obstruction.
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| 2. |
- Shakirova, Yulia, et al.
(författare)
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Human urinary bladder smooth muscle is dependent on membrane cholesterol for cholinergic activation.
- 2010
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 1879-0712 .- 0014-2999. ; 634, s. 142-148
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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