Department of Experimental Medical Science, Lund University, Biomedical Centre, BMC D12, SE-221 84 Lund, Sweden.
Eur J Pharmacol. 2010 Dec 15;649(1-3):362-8. doi: 10.1016/j.ejphar.2010.09.050. Epub 2010 Sep 22.
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.
器官肥大通常与 caveolins 的表达变化和膜上 caveolae 的密度改变有关。大量的信号中介物与 caveolae 相关，而 caveolae 的缺失对膀胱的收缩性有深远的影响。我们假设由膀胱流出道梗阻（BOO）引起的平滑肌肥大可能导致 caveola 密度改变，从而影响收缩调节。大鼠 BOO 6 周导致平滑肌 caveolae 的数量每 μm 膜增加了 2.56 倍。 caveolin-1 或 cavin-1 的表达与 β-肌动蛋白相比没有变化，但单位肌肉体积的膜面积降至 0.346。肥大与对 carbachol 的反应性收缩改变有关。胆固醇去吸附的作用，破坏脂筏和 caveolae，但对收缩的影响没有改变。在对照膀胱逼尿肌中，bradykinin 的收缩对 mβcd 有抵抗力，但在梗阻 6 周后被其抑制。结论是大鼠膀胱逼尿肌肥大导致单位膜面积 caveolae 的数量增加。这种变化是由于单位肌肉体积的膜面积减少所致，它对胆碱能激活不起作用，但在长期梗阻后促进 bradykinin 的收缩。
