Biochemical and functional correlates of an increased membrane density of caveolae in hypertrophic rat urinary bladder.
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 6 weeks 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 6 weeks 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.
Shakirova
Yulia
Y
Department of Experimental Medical Science, Lund University, Biomedical Centre, BMC D12, SE-221 84 Lund, Sweden.
Swärd
Karl
K
Uvelius
Bengt
B
Ekman
Mari
M
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1 / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006984:Hypertrophy; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism; D009119:Muscle Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism / Q000648:ultrastructure; D009465:Neuromuscular Agents / Q000494:pharmacology; D054799:Phospholipase C beta / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000503:physiopathology
C495537:Cav1 protein, rat; D051242:Caveolin 1; C506791:Cavin1 protein, rat; D008565:Membrane Proteins; D009465:Neuromuscular Agents; D016601:RNA-Binding Proteins; D043587:Receptor, Muscarinic M3; D002217:Carbachol; D054799:Phospholipase C beta; C518035:Plcb1 protein, rat; D001920:Bradykinin