Hypertrophy changes the muscarinic receptor subtype mediating bladder contraction from M3 toward M2
Hypertrophy changes the muscarinic receptor subtype mediating bladder contraction from M3 toward M2
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DOI：
10.1152/ajpregu.00009.2003
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发表时间：
2003-09-01
影响因子：
2.8
通讯作者：
Ruggieri, MR
中科院分区：
文献类型：
--
作者：
Braverman, AS;Ruggieri, MR
大鼠主要盆神经节电灼术（MPGE）和脊髓损伤诱导膀胱肥大和介导膀胱收缩的毒蕈碱受体亚型从主要M-3变为M-2和M-3的组合。为了确定这是否是膀胱肥大或去神经支配的结果，我们研究了以下组：假手术对照组、尿流改道（DIV）、MPGE联合尿流改道（DIV-DEN）、双侧MPGE（DEN）、膀胱出口梗阻（BOO）和MPG分散（MPG-DEC）。膀胱去神经支配的程度由归一化为对电场刺激的响应的最大卡巴胆碱响应来确定。免疫沉淀法测定受体亚型密度。亚型选择性毒蕈碱拮抗剂抑制卡巴胆碱诱导的收缩的亲和力用于确定亚型介导的收缩。与假手术组相比，DEN、MPG-DEC和BOO膀胱肥大，而DIV膀胱萎缩。假手术组、DIV组和DIV-DEN组的膀胱收缩由M-3受体亚型介导，而M-2受体亚型参与DEN组、MPG-DEC组和BOO组的收缩。肥大膀胱的总受体密度和M-2受体密度增加，而所有实验组的M-3受体密度均减少。因此，膀胱肥大，独立于膀胱去神经支配，导致毒蕈碱受体亚型介导的膀胱收缩从M-3向M-2的转变。
Major pelvic ganglion electrocautery (MPGE) and spinal cord injury in the rat induce bladder hypertrophy and a change in muscarinic receptor subtypes mediating bladder contraction from predominantly M-3 to a combination of M-2 and M-3. To determine whether this is a result of bladder hypertrophy or denervation, we studied the following groups: sham-operated controls, urinary diversion (DIV), MPGE together with urinary diversion (DIV-DEN), bilateral MPGE (DEN), bladder outlet obstruction (BOO), and MPG decentralization (MPG-DEC). The degree of bladder denervation was determined by the maximal carbachol response normalized to the response to electric field stimulation. Receptor subtype density was determined by immunoprecipitation. The affinity of subtype-selective muscarinic antagonists for inhibition of carbachol-induced contractions was used to determine the subtype-mediating contraction. DEN, MPG-DEC, and BOO bladders were hypertrophic whereas DIV bladders were atrophic compared with sham operated. Bladder contraction in sham-operated, DIV, and DIV-DEN was mediated by the M-3 receptor subtype, whereas the M-2 subtype participated in contraction in the DEN, MPG-DEC, and BOO groups. The hypertrophied bladders had an increase in total and M-2 receptor density while all experimental groups showed a reduction in M-3 receptor density. Thus bladder hypertrophy, independent from bladder denervation, causes a shift in the muscarinic receptor subtype mediating bladder contraction from M-3 toward M-2.